Download Erythropoiesis-Stimulating Agents (ESAs)

MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
Original Issue Date (Created):
7/1/2002
Most Recent Review Date (Revised):
3/29/2016
Effective Date:
1/1/2017
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Note: Throughout this policy, unless otherwise stated, the term “ESA” (erythropoiesis-stimulating
agents) refers to epoetin alfa (Epogen®, Procrit®), and darbepoetin alfa (Aranesp®).
The use of epoetin alfa, darbepoetin, or pegylated (PEG)-epoetin beta may be considered medically
necessary for:
 treatment of anemia associated with chronic kidney disease.a,b,c
The use of PEG-epoetin beta is investigational for all other indications. There is insufficient
evidence to support a conclusion concerning the health outcomes or benefits associated with these
procedures
The use of epoetin alfa or darbepoetin may be considered medically necessary for:
 treatment of anemia in cancer patients with non-myeloid malignancies where anemia is due
to the effect of concomitantly administered chemotherapy1,2;

treatment of anemia related to therapy with AZT (zidovudine) in HIV-infected patients1;

reduction of allogeneic blood transfusion in surgery patients1;

treatment of patients following allogeneic bone marrow transplantation; and

treatment of patients with myelodysplastic syndromes to reduce transfusion dependency.

treatment of patients with hepatitis C and anemia related to ribavirin treatment.
In the medically necessary conditions noted above, the following criteria also apply:

The lowest dose of ESAs should be used in order to avoid red blood cell transfusions,

ESAs should not be used to raise the Hb level above 12 g/dL, and

ESA therapy should not be administered without adequate iron stores.
For the medically necessary use in cancer patients, these additional FDA criteria also apply:
 Epoetin or darbepoetin therapy should not be initiated at Hb levels ≥10 g/dL and
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MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111

Epoetin or darbepoetin treatment should be discontinued following the completion of a
myelosuppressive chemotherapy course.
1
2
FDA-approved label for epoetin alfa (Epogen®, Procrit®)
FDA-approved label for darbepoetin alfa (Aranesp®)
The use of epoetin alfa or darbepoetin is considered investigational for:
 Treatment of patients following high-dose chemotherapy with autologous stem-cell
support.
 Treatment of non-iatrogenic chronic anemia of cancer;
 Other cancer-associated anemia excepted as noted in the policy section
 Treatment of orthostatic hypotension
There is insufficient evidence to support a conclusion concerning the health outcomes or
benefits associated with these procedures.
a FDA-approved
label for epoetin alfa (Epogen®, Procrit®).
label for darbepoetin alfa (Aranesp®).
c FDA-approved label for PEG-epoetin beta (Mircera®).
b FDA-approved
Policy Guidelines
Non-myeloid malignancies include solid tumors and the non-myeloid hematologic malignancies
myeloma, lymphoma, and chronic lymphocytic leukemia.
Administration
ESAs and pegylated (PEG)-epoietin beta are to be administered according to current FDAapproved labeling for each product, using recommended Hb levels for starting, stopping, and dose
adjustment. This includes decreasing the dose of ESA as the Hb approaches the target level.
Prior to commencing ESA or PEG-epoietin beta therapy, the patient’s iron stores, blood ferritin,
and transferrin saturation should be evaluated, adjusted, and maintained within normal
physiological limits. ESA therapy should not be administered without adequate iron stores.
Blood Pressure Monitoring
Blood pressure should be adequately controlled prior to initiation of ESA therapy and closely
monitored and controlled during treatment ESAs and PEG-epoetin beta are contraindicated in
patients with uncontrolled hypertension.
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MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
Discontinuation
Erythropoiesis-Stimulating Agents
Patients with myelodysplastic syndromes should be initially limited to a 3-month trial period with
ESA. If no response to ESA is observed, ongoing therapy would be futile.
ESAs and PEG-Epoetin Beta
Patients with chronic kidney disease who do not respond adequately over a 12-week dose escalation
period should not have their ESA or PEG-epoetin beta dose increased further. Increasing ESA or
PEG-epoetin beta dose further is unlikely to improve response and may increase risks; the lowest
ESA or PEG-epoetin beta dose that maintains adequate Hb to avoid recurrent red blood cell
transfusions should be used. Other causes of anemia should be evaluated. If responsiveness does not.
Risk Evaluation and Mitigation Strategy
Epoetin alfa and darbepoetin must be prescribed and dispensed in accordance with a risk evaluation
and mitigation strategy (REMS) drafted by the manufacturer and approved by FDA.1
REMS for epoetin alfa and darbepoetin alfa each comprises elements to assure safe use and an
implementation system.


ESA manufacturers must ensure that all hospitals and healthcare professionals who prescribe
and/or dispense ESAs to patients with cancer have enrolled and completed training in the
ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe
use of ESAs) Oncology Program. The ESA APPRISE program began on March 24, 2010
after FDA’s initial approval of separate but similar REMS for epoetin alfa and darbepoetin
alfa on February 16, 2010. Both REMS were subsequently modified, most recently on
December 31, 2013.
Healthcare providers and hospitals that prescribe and/or dispense an ESA for chronic kidney
disease (CKD) must provide each patient with a copy of the REMS Medication Guide
included in the product label and ensure that patients are adequately informed of the risks
associated with ESA treatment. However, prescribers are not required to enroll in and
complete the ESA APPRISE program.
PEG-epoetin beta does not have a REMS.
On March 27, 2012, FDA approved a REMS for peginesatide with a communication plan as its only
component. The plan’s goal was to inform all healthcare professionals who might prescribe the drug
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MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
that peginesatide is indicated only for adult patients with CKD on dialysis, and of potentially fatal
risks associated with its use in CKD patients not on dialysis. Peginesatide is currently discontinued.
Cross-reference:
MP-2.103 Off-Label Use of Medications
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
BlueJourney HMO*
BlueJourney PPO*
FEP PPO**
* Refer to Centers for Medicare and Medicaid (CMS) National Coverage Determination (NCD)
110.21 Erythropoiesis-Stimulating Agents (ESA’s) in Cancer and Related Neoplastic Conditions.
Also refer to the Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy
Chapter 15, section 50.5.2 for coverage of ESA’s for end-stage renal disease related anemia.
** For Procrit and Epogen - Refer to FEP Medical Policy Manual MP-5.10.16 EPOGEN /
PROCRIT; for Aranesp refer to MP-5.10.01Aranesp. The FEP Medical Policy manual can be found
at: www.fepblue.org
III. DESCRIPTION/BACKGROUND
TOP
EPO is a glycoprotein hematopoietic growth factor synthesized by cells near the renal tubules in
response to changes in the blood oxygen concentration. When a patient is anemic, the ability of the
blood to carry oxygen is decreased. An oxygen-sensing protein in the kidney detects the decrease in
blood oxygen concentration and induces the production of EPO, which then acts on the erythroid
cell line in the bone marrow to stimulate hematopoiesis, thereby effectively increasing blood Hb
concentrations. Suppression of erythropoietin production or suppression of the bone marrow
response to erythropoietin results in anemia in several disease processes, including chronic kidney
disease (CKD), many types of cancer treatment, other chronic diseases, and use of certain drugs.
The severity of anemia is defined by blood Hb concentration. Normal ranges are 12 to 16 g/dL in
women and 14 to 18 g/dL in men. Mild anemia is defined as Hb from 10 g/dL to the lower limit of
normal ranges, moderate anemia is 8 to 10 g/dL, and severe anemia is 8 g/dL or less.
ESAs are produced using recombinant DNA technologies. They were initially developed as
replacement therapy to treat anemia due to endogenous erythropoietin deficiency that commonly
occurs in patients with CRF secondary to CKD. Patients with CRF will become severely anemic and
experience severe fatigue and reduced exercise tolerance unless treated with blood transfusions or an
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POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ESA. Partial correction of anemia by ESA treatment of patients with CRF reduces the need for red
blood cell (RBC) transfusions and enhances physical functioning.
In cancer, anemia occurs with varying degrees of frequency and severity. It occurs most commonly
in genitourinary, gynecologic, lung, and hematologic malignancies. Anemia may be directly related
to cancer type or to its treatment. Oncologic anemia occurs by a variety of mechanisms: (1) Poor oral
intake or altered metabolism may reduce nutrients (folate, iron, vitamin B12) essential for RBC
production. (2) Antibodies and/or immunoregulatory abnormalities associated with certain tumor
types (most commonly, B cell malignancies) may cause increased erythrocyte destruction
(hemolysis). (3) Tumors may cause blood loss via tissue invasion, for example gastrointestinal
bleeding from colon cancer. (4) Other neoplasms, particularly hematologic malignancies (leukemia,
lymphoma, multiple myeloma) can invade the bone marrow and disrupt the erythropoietic
microenvironment. (5) In more advanced cases, there may be marrow replacement with tumor or
amyloid. (6) However, marrow dysfunction can occur even in the absence of frank invasion. (7)
Inflammatory proteins from interactions between the immune system and tumor cells are thought to
cause inappropriately low erythropoietin production and poor iron utilization, as well as a direct
suppression of RBC production. Cancer treatments also may cause anemia: (1) radical cancer
surgery can result in acute blood loss; and (2) radiotherapy and many cytotoxic chemotherapeutic
agents suppress marrow to varying degrees. Damage is due to a variety of mechanisms. For example,
alkylating agents cause cumulative DNA damage; antimetabolites damage DNA indirectly; and
platinum-containing agents appear to damage erythropoietin-producing renal tubule cells.
RBC transfusion is the traditional approach to quickly ameliorate anemia symptoms. However, this
approach carries risk for several potential adverse events. The highest adverse event risk (1 per 432
whole blood units transfused) is for transfusion-related acute lung injury (TRALI). Adverse events
due to errors in transfusion (e.g., type mismatch) are estimated to occur at a rate of 1 per 5000 to
10,000 units of blood transfused. Current transfusion medicine and blood bank practices have
significantly reduced the risk of transmissible infections, primarily due to better donor selection and
screening for infectious diseases. Estimated risks per unit of blood transfused for transmission of
hepatitis B virus (<1 in 400,000), hepatitis C virus (<1 in 1,000,000), HIV (<1 in 1,000,000), and
bacterial contaminants (1 per 10,000 to 100,000) have fallen dramatically since the early 1990s.
Therefore, although the initial impetus to commercialize erythropoietin replacement products was
based on reduction in the risks associated with blood transfusion, current practices have mitigated
many of those risks. Nonetheless, blood shortages, transfusion errors, and risks of alloimmunization
and TRALI provide sufficient rationale for the use of ESA therapy in appropriately indicated
patients.
Four ESA products have been licensed in the United States:

Epoetin alfa is manufactured, distributed, and marketed by Amgen, Inc. under the proprietary
name, Epogen®. The same epoetin alfa product manufactured by Amgen Inc. is also
marketed and distributed by Janssen Products, LP, a subsidiary of Johnson and Johnson,
under the proprietary name, Procrit®. Under a contractual agreement with Amgen, Janssen
Products LP has rights to develop and market Procrit® for any indication other than for
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MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111



treatment of anemia associated with CRF in patients on dialysis or use in diagnostic test kits.
Epogen® and Procrit® have identical labeling information for all FDA-approved indications.
A second ESA, darbepoetin alfa, is marketed solely by Amgen, under the proprietary name,
Aranesp®.
The third ESA product, peginesatide, was codeveloped and commercialized by Affymax Inc.
and Takeda Pharmaceuticals, who market it under the proprietary name, Omontys®. In
February 2013, Affymax, Takeda, and FDA announced a voluntary recall of all lots of
peginesatide due to postmarketing reports of serious hypersensitivity reactions, including
anaphylaxis. FDA currently lists peginesatide (Omontys®) as discontinued.
Epoetin beta was unavailable in the U.S. However, a methoxy pegylated (PEG) form of
epoetin beta, called “continuous erythropoietin receptor activator” or CERA, has a prolonged
half-life that permits once monthly dosing. PEG-epoetin beta was FDA-approved in 2007
and was marketed outside the U.S. by Hoffmann-LaRoche under the proprietary name
Mircera®. Due to a copyright infringement lawsuit brought by Amgen in 2009, U.S. sales
were prohibited until mid-2014.
Epoetin alfa and epoetin beta have the same amino acid sequence as endogenous erythropoietin but
differ from each other in glycosylation2; clinical effects are considered interchangeable.2,3
Darbepoetin alfa is similar to endogenous erythropoietin but has 2 additional oligosaccharide chains.
In contrast, peginesatide lacks any amino acid sequence homology to erythropoietin. It is a synthetic
dimer of identical 21-amino acid peptides bound to a linker and to polyethylene glycol, with a total
molecular weight of approximately 45,000 Da. (The molecular weight of endogenous erythropoietin
is approximately 34,000 Da.) However, the epoetins, darbepoetin, and peginesatide all have
pharmacologic actions similar to those of the endogenous hormone. Each binds to and activates the
human erythropoietin receptor and thus increases the number of RBCs and the blood concentration
of hemoglobin, when given to individuals with functioning erythropoiesis. Both epoetin alfas, PEGepoetin beta, and darbepoetin are FDA-approved to treat anemia in patients with CKD who are on
dialysis or not on dialysis. Peginesatide is approved only for adult patients with anemia from CKD
who are on dialysis. Epoetin alfa and darbepoetin also are approved for other indications (see Policy
section).
REGULATORY STATUS
The major regulatory timelines for approval actions pertaining to new indications are summarized
next:
Epoetin alfa (Epogen®/Procrit®):
1989: Approved for use in patients with anemia due to CRF
1991: Approved for use in zidovudine-treated, HIV-infected patients
1993: Approved for chemotherapy-induced anemia in patients with nonmyeloid malignancies
1996: Approved for presurgical use in certain patients undergoing surgery
Darbepoetin alfa (Aranesp®):
2001: Approved for use in patients with anemia due to CRF
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POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
2002: Approved for chemotherapy-induced anemia in patients with nonmyeloid malignancies
Peginesatide (Omontys®):
2012: Approved for use in adults with anemia due to CKD who are on dialysis
2013: Voluntary recall of all lots due to postmarketing reports of serious hypersensitivity
Methoxy polyethylene glycol (PEG) epoetin-beta (Mircera®)



2007: Approved for use in patients with anemia due to CRF who are on dialysis or not on
dialysis
2009: Injunction prohibiting U.S. sales until mid-2014 due to copyright infringement
2014: Resumption of U.S. sales anticipated
IV. RATIONALE
TOP
Two 1995 TEC Assessments (Myelodysplastic Syndrome and Chronic Anemia of Cancer - Tab 10;
Allogeneic Bone Marrow Transplantation or High-Dose Chemotherapy with Autologous Stem-Cell
Support - Tab 11) provided the basis for the original policy statements regarding these two settings.
Primary data sources for oncology included a 2006 comparative meta-analysis on the outcomes of
epoetin or darbepoetin for managing anemia in patients undergoing cancer treatment prepared for the
Agency for Healthcare Research and Quality (AHRQ) and the 2005 AHRQ report, updated in 201335
; a meta-analysis using individual patient data for outcomes of erythropoiesis-stimulating agent
(ESA) therapy in patients with cancer,6,7 with additional outcomes reported in 20128; American
Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) 2010 clinical practice
guidelines on the use of epoetin and darbepoetin to treat chemotherapy-associated anemia9; 2007
briefing documents available from the U.S. Food and Drug Administration (FDA) Oncologic Drugs
Advisory Committee (ODAC)2; and a 2007 Decision Memorandum from the Centers for Medicare
and Medicaid Services on the use of ESAs for nonrenal disease indications.10
Information on the use of ESAs in chronic renal failure (CRF) was obtained from several sources
including 2007 briefing documents from a joint meeting of FDA’s Cardiovascular and Renal Drugs
Advisory Committee (CRDAC) and Drug Safety and Risk Management Advisory Committee
(DSRMAC) to reassess ESA risks11; and, a meta-analysis of blood hemoglobin (Hb) targets for
patients with CRF-associated anemia.12 FDA-approved labels for ESAs available (or soon to be
available) in the United States comprised additional data sources for this Policy, in particular,
recommended dosing information for the different clinical settings covered.13-16
The 2010 ASCO/ASH clinical practice guideline for the use of ESAs considers epoetin and
darbepoetin, used at dosages recommended in current FDA-approved package inserts, to be
equivalent with respect to effectiveness and safety. Epoetin and darbepoetin are identical with
respect to: (1) indications for use in chemotherapy-induced anemia, (2) Hb limits for adjusting doses,
initiating or discontinuing treatment, (3) warnings and cautions to consider, and (4) increased rates
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ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
of thromboembolic events in the experimental arms of separate trials on each product versus
controls/placebo.9
Chronic Kidney Disease (Chronic Renal Failure)
Epoetin Alfa, Epoetin Beta, and Darbepoetin
At initial approval of epoetin in 1989, the primary objective of treatment was to raise Hb
concentration sufficiently to avoid transfusion, with a target range of 9 to 10 g/dL in anemic patients
with chronic kidney disease (CKD). The first National Kidney Foundation Kidney Disease
Outcomes Quality Initiative (NKF-KDOQI) guidelines in 1997 recommended an Hb concentration
of 11 g/dL, a level that was increased by subsequent NKF-KDOQI anemia guidelines, to 11 to 13
g/dL in 2007.17 With increased experience in the use of ESAs, it became unclear whether higher Hb
target concentrations, including normalization, would yield additional benefits, in particular in
physical function and improved cardiovascular outcomes. Clinical doubts increased with publication
of the first large randomized controlled trial (RCT) of Hb normalization using epoetin alfa in
hemodialysis patients (Normal Hematocrit Cardiac Trial [NHCT]).18 NHCT showed a trend toward
increased mortality risk and significantly increased risk for vascular access thrombosis with ESA
treatment to a hematocrit (Hct) target of 42%. Subsequently, 4 published RCTs in hemodialysis
patients with end-stage renal disease (ESRD) and 8 in nondialysis patients with CKD found
improved physical function at higher Hb targets, but none demonstrated significant improvements in
cardiovascular end points or mortality.19
The Epogen®/Procrit® label was modified in 1996 to include results of the NHCT study that
showed a higher mortality rate for anemic dialysis patients randomized to an Hct of 42%, compared
with an Hct of 30%. Ten years later, the CHOIR study reported worse cardiovascular outcomes for
anemic CRF patients who were not undergoing dialysis and who were randomized to a target Hb of
13.5 g/dL, compared with an Hb of 11.3 g/dL.20 Subsequent analyses of outcomes in CHOIR
showed shorter times to progression of kidney disease and higher rates of renal replacement therapy
and death among patients randomized to the higher Hb target.21 The CREATE study, also reported in
2006, was similar to CHOIR but enrolled fewer patients.22 CREATE did not demonstrate statistically
significant differences in adverse cardiovascular outcomes for the higher Hb group, but the general
trend of major cardiovascular outcomes was similar to the CHOIR findings. The 2009 TREAT study
randomized 4038 patients with type 2 diabetes mellitus, Hb of 11 g/dL or less, and CKD not on
dialysis.23 Patients in 1 arm were treated with darbepoetin to a target Hb of 13 g/dL, and those in the
other arm received darbepoetin only if Hb fell below 9 g/dL. Risks for 2 end points were not
significantly different between arms: death or a cardiovascular event (hazard ratio [HR], 1.05; 95%
confidence interval [CI], 0.94 to 1.17; p=0.41) and death or ESRD (HR=1.06; 95% CI, 0.95 to 1.19;
p=0.29). However, fatal or nonfatal stroke was significantly increased among patients randomized to
the higher Hb target (HR=1.92; 95% CI, 1.38 to 2.68; p<0.001). Multivariate analysis found no
statistically significant relationship of increased stroke risk to any baseline characteristic; to effects
on blood pressure, Hb, or platelet count; or to darbepoetin dose.24
A 2012 meta-analysis by Vinhas et al included only large RCTs (N >500) with a minimum duration
of 1 year.25 Outcomes of interest were vascular access thrombosis, stroke, progression to ESRD, and
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ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
all-cause mortality. Five trials (7902 patients), including the CHOIR, CREATE, NHCT, and TREAT
trials, were identified. Mean or median follow-up duration ranged from 14 to 36 months. As shown
in Table 1, higher Hb targets were associated with increased risks of vascular access thrombosis and
stroke but not with progression to ESRD or all-cause mortality.
Table 1. Results of Meta-Analysis by Vinhas et al25
Outcome
n/N
Relative Riska
95% CI
I2,b
Vascular access thrombosis 2/1829
1.34
1.16 to 1.55
0%
Stroke
4/7305
1.74
1.32 to 2.28
0%
Progression to ESRD
3/6073
1.09
0.99 to 1.20
0%
All-cause mortality
5/7902
1.15
0.98 to 1.35
0%
CI: confidence interval; ESRD: end-stage renal disease; n/N: number of trials/number of patients.
a Relative risk for outcome at higher Hb targets (13.0-15.0 g/dL) compared with lower Hb targets (9.5-11.5 g/dL).
b Describes the proportion of total variation across studies that is due to heterogeneity rather than chance.
In 2012, the American Society of Nephrology released its evidence-based recommendations for the
“Choosing Wisely” campaign to improve patient care and resource use.26 Citing the evidence
reviewed here, the society included the following among its top 5 recommendations: “Do not
administer erythropoiesis-stimulating agents to CKD patients with hemoglobin levels ≥10 g/dL
without symptoms of anemia.”
A 2014 Cochrane review included 8 trials (total N=2051) that compared darbepoetin with epoetin
(alfa or beta) in adults with anemia due to CKD.27 No statistically significant differences were
observed in random effects meta-analyses of final Hb or mean change in Hb level, overall mortality,
cardiovascular events or cardiovascular mortality, blood transfusions, or adverse events due to
hypertension or vascular access thrombosis. Risk of bias was rated as moderate to high, and
statistical heterogeneity was minimal (I2=0%) for all outcomes.
Pegylated Epoetin Beta
FDA’s 2007 approval of PEG-epoetin beta (Mircera®) was based on 6 phase 3, international, openlabel, RCTs in patients with anemia due to CKD16 (see Table 2). In 2 trials (total N=505), patients
were not receiving ESA therapy (correction trials), and in 6 trials (total N=1894), Hb was stable on
maintenance ESA therapy (maintenance trials). All but1 trial (ARCTOS) enrolled dialysis-dependent
patients. The primary efficacy outcome in all trials was maintenance of Hb levels over 24 to 52
weeks, adjusted for baseline Hb and center, in the intent-to-treat and per protocol patient samples.
For this outcome, the trials demonstrated noninferiority of PEG-epoetin beta once or twice monthly
to epoetin (alfa or beta) 1 to 3 times weekly (AMICUS, MAXIMA, PROTOS, RUBRA) and to
darbepoetin weekly or twice monthly (ARCTOS and STRIATA). In the correction trials (ARCTOS
and AMICUS), median time to response was longer in the PEG-epoetin beta groups (43 days and 57
days, respectively) compared with the darbepoetin (29 days) and epoetin (31 days) groups.
Although target Hb ranges in these trials included levels that have since been associated with
increased mortality in CKD (i.e., >11 g/dL),28 FDA’s summary review of safety (based on 1789
PEG-epoetin beta-treated patients [64% for >1 year] and 948 ESA-treated patients) reported that
mortality was similar between the 2 groups (10% vs 11%, respectively).29 Incidence of serious
adverse events also was similar between groups (37% vs 40%, respectively), although serious
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POLICY NUMBER
MP-2.111
bleeding events (5.2% vs 4%), serious gastrointestinal bleeding events (1.2% vs 0.2%), and
thrombocytopenia less than 100109 platelets/L (7.5% vs 4.4%) occurred more commonly in PEGepoetin beta-treated patients. FDA reviewers attributed these imbalances to the greater proportion of
patients on hemodialysis in the PEG-epoetin beta group (84% vs 80%), and considered the risks of
hemorrhage and thrombocytopenia similar to or slightly increased above that for other ESAs. Trials
excluded patients with poorly controlled hypertension; 27% of enrolled patients required increases in
antihypertensive therapy.16
Table 2. Pivotal Trials of PEG-Epoetin Beta
N
Initial Dose
Results
%
Respondersa
Mean
ΔHb,b g/dL
Correction trials in patients not receiving ESA therapy
Macdougall 2008 (ARCTOS)30,c
PEG-epoetin beta
162
98
2.15
0.6 /kg SC q2wk
Darbepoetin
162
96
2.00
0.45 /kg SC qwk
P value
<0.001d
<0.001e
Klinger 2007 (AMICUS)31
PEG-epoetin beta
135
93
2.70
0.4 /kg IV q2wk
Epoetin alfa/beta
46
91
2.56
Per product label IV 3/wk
P value
<0.001d
<0.001e
Maintenance trials in patients receiving ESA therapy
Levin 2007 (MAXIMA)32
PEG-epoetin beta IV q2wk
223
‒
-0.71
PEG-epoetin beta IV q4wk
224
‒
-0.25
Epoetin alfa/beta IV q1-3x/wk
226
‒
-0.75
P value vs control
‒
<0.001ef
Sulowicz 2007 (PROTOS)33
PEG-epoetin beta SC q2wk
190
76
-0.03
 PEG-epoetin beta dose
PEG-epoetin beta SC q4wk
191
66
-0.13
based on maintenance
Epoetin alfa/beta SC q1-3x/wk
191
72
-0.11
ESA dose
P value vs control
‒g
<0.001ef
Canaud 2008 (STRIATA)34
 Comparator ESA dose
PEG-epoetin beta IV q2wk
157
66
0.06
was continuation of
Darbepoetin IV q1-2wk
156
72
-0.12
maintenance dose
P value
0.25h
<0.001e
Spinowitz 2008 (RUBRA)35
PEG-epoetin beta SC/IV q2wk
168
69
0.09
Epoetin alfa/beta SC/IV q1-2wk
168
68
-0.03
P value
‒i
<0.001e
ESA: erythropoiesis-stimulating agents; Hb: hemoglobin; IV: intravenous; PEG: pegylated; q2wk: every 2 weeks; q4wk:
every 4 weeks; SC: subcutaneous.
a Defined as:

ARCTOS: Hb level ≥11 g/dL and increased ≥1.0 g/dL from baseline at 28 wk; target Hb 11-13 g/dL

AMICUS: Hb level ≥11 g/dL and increased ≥1.0 g/dL from baseline at 24 wk; target Hb 11-13 g/dL

PROTOS, STRIATA: Mean Hb within ±1 g/dL of baseline values through 52 wk; target Hb 10-13.5 g/dL
b Change from baseline Hb at 24 wk (AMICUS), 28 wk (ARCTOS), 36 wk (MAXIMA, STRIATA, RUBRA), or 52 wk
(PROTOS).
c Patients with stage 3 or 4 CKD (creatinine clearance <59 mL/min) who were not on dialysis.
d For noninferiority to a predefined minimum of 60%.
e For noninferiority to comparator; noninferiority margin for difference in mean Hb level (PEG-epoetin beta minus
comparator), -0.75 g/dl.
f Both comparisons.
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g
Trial investigators did not report statistical testing. Neither PEG-epoetin beta group was statistically different from
comparator by 2 test (author calculation; p=0.52 for q2wk PEG-epoetin beta, p=0.36 for q4wk PEG-epoetin beta).
h Chi-square test.
i Trial investigators did not report statistical testing. There was no statistical difference between groups by 2 test (author
calculation; p=0.88).
A 2014 Cochrane review included random effects meta-analyses of the 5 trials in dialysis patients
listed in Table 2 and reported no statistical between-group differences in final Hb level (compared
with epoetin), overall mortality, blood transfusions, or adverse events due to hypertension or
vascular access thrombosis.36 In the STRIATA trial, final Hb level was statistically higher in the
PEG-epoetin group compared with the darbepoetin group (mean difference, 0.30 g/dL [95% CI, 0.05
to 0.55]). Risk of bias was rated as low to moderate, and statistical heterogeneity was low to
moderate (I2 range, 0%-34%).
Since FDA approval, subsequent short-term trials (24-40 weeks; total N=841) have replicated the
findings of the pivotal correction trials in patients on hemodialysis37 and not on hemodialysis,38,39
and of the pivotal maintenance trials in patients on hemodialysis.40,41 Of 324 nondialysis patients in
the ARCTOS correction trial, 296 (96%) entered a 24-week extension study.42 Patients who
responded to PEG-epoetin beta biweekly (n=145) were rerandomized 1:1 to biweekly or monthly
dosing to maintain Hb between 11 to 13 g/dL. Mean (SD) Hb levels were 11.9 (0.9) g/dL, 11.7 (0.9)
g/dL, and 11.9 (1.0) g/dL in the PEG-epoetin biweekly, PEG-epoetin monthly, and darbepoetin
(weekly or biweekly) groups (n=151), respectively. Within-patient variation in Hb levels was similar
across groups.
Peginesatide
FDA approved Omontys® (peginesatide) to treat anemia in CKD patients on dialysis in March 2012
based on 2 randomized active-controlled noninferiority trials, which were summarized in a TEC
Specialty Pharmacy Report.43 The first trial, EMERALD-1, enrolled 803 patients in the United
States, and controls received epoetin alfa (Epogen®, Procrit®). The second trial, EMERALD-2,
enrolled 823 patients in the United States and Europe, and controls received epoetin alfa or epoetin
beta (not available in the United States). Adults on dialysis for at least 3 months with stable Hb
concentrations (between 10.0 g/dL and 12.0 g/dL) on ESA therapy for at least 8 weeks were eligible
for randomization to peginesatide once monthly or continued epoetin 1 to 3 times weekly for 36
weeks. Results for the primary efficacy outcome (between-arm difference of the change from
baseline Hb to the mean value during weeks 29 to 36 [the evaluation period], with a noninferiority
margin of -1.0 g/dL) demonstrated the noninferiority of peginesatide in each trial (-0.15 g/dL in
EMERALD-1, +0.10 in EMERALD-2). The relative risk (RR) for red blood cell (RBC) transfusion
also did not differ significantly between arms (RR=1.21; 95% CI, 0.76 to 1.92 in EMERALD 1;
RR=0.79; 95% CI, 0.50 to 1.24 in EMERALD-2).
Two other trials (PEARL-1 and PEARL-2; total N=656 randomized to peginesatide, N=327 to
darbepoetin) were conducted for patients with CKD who were not on dialysis. The trials
prospectively evaluated cardiovascular risk of ESAs. The 4 trials together were powered for a
primary safety outcome, which was to rule out an increase of 30% or more in the risk of the
composite safety end point, based on a 2-sided 90% CI. The composite safety end point comprised
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death, stroke, myocardial infarction, and hospitalization for congestive heart failure, unstable angina
or arrhythmia. Incidence of the composite safety outcome did not differ significantly between groups
randomized to peginesatide or active comparator (HR=1.06; 95% CI, 0.89 to 1.26). In an analysis
limited to the 2 trials of patients on dialysis (EMERALD-1 and -2), the 2 groups again did not differ
with respect to incidence of the composite safety end point (HR=0.95; 90% CI, 0.79 to 1.13).
However, peginesatide significantly increased the incidence of this composite safety end point in a
pooled analysis of the 2 trials for patients not on dialysis (PEARL-1 and -2; HR=-1.32; 90% CI, 1.02
to 1.72). Cardiovascular harms in the nondialysis population were considered unacceptably high and
the indication was abandoned. The risk evaluation and mitigation strategy (REMS) communication
plan developed by the manufacturer and approved by FDA (see Policy Guidelines section) was
designed to inform health care providers who might prescribe peginesatide of these findings. Note
also that thus far, no data are available on safety or efficacy of peginesatide for any other ESA
indications (e.g., patients with a nonmyeloid malignancy who are anemic while receiving palliative
chemotherapy, HIV patients who are anemic while receiving zidovudine, or perisurgical patients
unable to donate autologous blood).
On February 23, 2013, Affymax, Takeda, and FDA announced a voluntary recall of all lots of
peginesatide due to postmarketing reports of serious hypersensitivity reactions, including
anaphylaxis.44 Serious reactions occurred within 30 minutes of the first dose of peginesatide; serious
reactions after subsequent doses have not been reported. Among approximately 25,000 patients who
received peginesatide postapproval, the estimated overall incidence of hypersensitivity reactions was
2 per 1000, and the estimated incidence of fatal reactions was 2 per 10,000. FDA currently lists
peginesatide (Omontys®) as “Discontinued” on its website (Drugs@FDA).
Section Summary
Three ESAs are FDA-approved for use in patients with CRF: epoetin alfa, pegylated epoetin beta
(PEG-epoetin beta), and darbepoetin alfa; PEG-epoetin beta is expected to be available in the U.S.
soon. Placebo-controlled clinical trials have established that epoetin alfa and darbepoetin alfa
effectively increase Hb concentrations and decrease the need for blood transfusions. Evidence does
not support an improvement in other clinical outcomes such as mortality, morbidity, functional
status, or quality of life (QOL). Some trials and a meta-analysis published in 2012 have reported
increased cardiovascular events and/or increased mortality in patients treated with ESAs. These trials
generally have treated to a Hb of 12 g/dL or higher. The optimal target Hb is unclear, and it is
uncertain whether treating to lower Hb levels avoids the increase in adverse events. Both
peginesatide and PEG-epoetin beta have been compared with other ESAs in randomized trials.
Peginesatide has shown noninferiority to epoetin for adult patients with CRF on dialysis. There are
no trials reporting benefit for peginesatide for other indications or in pediatric patients with kidney
disease. Currently, peginesatide is unavailable and should not be used. PEG-epoetin beta has shown
noninferiority to epoetin and darbepoetin for correcting or maintaining Hb levels in RCTs of patients
on dialysis or not on dialysis. In meta-analyses of trials in dialysis patients, no statistical differences
were reported in overall mortality, blood transfusions, or adverse events due to hypertension or
venous access thrombosis. PEG-epoetin beta currently is unavailable in the U.S.
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Oncology
Epoetin Alfa, Epoetin Beta, and Darbepoetin
In 1993, FDA approved Procrit®/Epogen® (epoetin alfa) to treat anemia in patients receiving cancer
chemotherapy based on data from 2 multicenter randomized placebo-controlled, double-blind
clinical trials; 1 enrolled 344 adult patients and the second enrolled 222 pediatric patients, and an
additional pooled analysis of 6 smaller double-blind RCTs enrolled a total of 131 patients. Patients
in all 3 studies received at least 12 weeks of concurrent chemotherapy and were randomized (1:1) to
receive Procrit®/Epogen® or placebo subcutaneously for 12 weeks. Overall, the data showed a
reduction in the proportion of patients requiring blood transfusion during the second and third
months of epoetin treatment.
The approval of Aranesp® (darbepoetin alfa) in 2002 for the treatment of anemia associated with
cancer chemotherapy was based on demonstration of a significant reduction in the proportion of
patients transfused during chemotherapy from week 5 through the end of treatment. Study 980297, a
phase 3, double-blind, placebo-controlled randomized (1:1) multicenter, multinational trial of
darbepoetin alfa enrolled 314 anemic patients with previously untreated non-small cell or small cell
lung cancer receiving at least 12 weeks of platinum-containing chemotherapy.
After the first approval of an ESA) for treatment of chemotherapy-associated anemia in 1993,
additional data became available regarding increased risks of mortality and possible tumor
promotion from the use of ESAs. Increased mortality has been observed in patients with cancer
(BEST, ENHANCE, 20000161, EPO-CAN-20 studies) when ESA treatment strategies were
designed to achieve and maintain Hb levels above 12 g/dL.9 In addition, ESA treatment strategies
intended to achieve and maintain Hb levels above 12 g/dL have demonstrated poorer tumor
outcomes (BEST, ENHANCE, DAHANCA studies). More recently, a 2009 meta-analysis using
individual patient data on 13,933 subjects from 53 RCTs reported significantly greater on-study
mortality (HR=1.17; 95% CI, 1.06 to 1.30) and poorer survival to end of follow-up (HR=1.06; 95%
CI, 1.00 to 1.12), with little heterogeneity between trials.6,7 Results were qualitatively similar when
the analysis was limited to 10,441 patients receiving concurrent chemotherapy in 38 trials, and there
was little evidence for a difference between trials of patients receiving different chemotherapy
regimens.
Data from multiple trials, consistent with data presented to ODAC in May 2004, led to revised
product labeling with broader and more detailed warnings against ESA treatment strategies targeting
Hb levels above 12 g/dL. More recent data, including the individual patient data meta-analysis
summarized earlier,6,7 suggested that factors such as the planned Hb ceiling for stopping ESA
therapy had little influence on increased mortality resulting from ESA treatment. Although risks of
Hb targets greater than needed to avoid transfusions are now well-established, data from adequate,
well-controlled studies employing recommended ESA doses and Hb targets are as yet insufficient to
assess effects on survival or tumor promotion. The only data provided to FDA which used the
recommended dose and Hb target was from Amgen Study 20010103, which demonstrated
significantly shorter survival in cancer patients receiving ESAs compared with those supported by
transfusion alone. However, this study was not adequately designed to assess effects on tumor
promotion or on thrombotic risks.
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Despite these caveats, data from available studies were sufficient for FDA to reassess the safety of
ESAs in patients with cancer and to re-evaluate the net clinical benefit of ESAs in this setting.
Results of the updated AHRQ comparative effectiveness review (2013) were consistent with those
reported in 2006.3 Among patients receiving chemotherapy and/or radiotherapy for malignancy, use
of ESAs to treat anemia reduced the risk of transfusion and increased the risk of thromboembolic
events and on-study mortality. Both thromboembolic events and on-study mortality were reduced
(but not eliminated) when ESA treatment was initiated at Hb less than 10 g/dL. Although the
reviewed evidence incorporated higher baseline and target Hb levels than those currently
recommended, sensitivity analyses suggested that these findings were robust. QOL, as assessed by
the Functional Assessment of Cancer Therapy (FACT) fatigue scale, was improved in patients
receiving ESAs, but the magnitude of improvement was less than the minimal clinically important
difference of 3 points. Fifteen included trials did not support an association between ESA use and
tumor response or progression; meta-analysis was not possible due to varying outcome definitions.
The AHRQ update incorporated the individual patient data meta-analysis previously described.6,7
Despite differing inclusion criteria and methodologies, additional analyses of these data by Tonia et
al (2012)8 supported results of the updated AHRQ review, as shown in Table 3.
Table 3. 2013 AHRQ Report and 2012 Individual Patient Data: Comparison of Updated Results
2013 AHRQ3
2012 Individual Patient Data8
n/N
Result (95% CI)
n/N
Result (95% CI)
Transfusions, RR
38/10,809
0.58 (0.53 to 0.64)
70/16,093
0.65 (0.62 to 0.68)
Thromboembolic events, RRa
37/12,570
1.51 (1.30 to 1.74)
57/15,278
1.52 (1.33 to 1.73)
On-study mortality, HRa
37/11,266
1.17 (1.04 to 1.31)
70/15,935
1.17 (1.06 to 1.29)
Tumor response, RRa
15/5577
Not pooledb
15/5012
1.02 (0.98 to 1.06)
FACT-fatigue, mean difference
14/3643
2.74c (1.69 to 3.78)
18/4965
2.08c (1.43 to 2.72)
Overall survival, HR for death
44/14,278
1.04 (0.99 to 1.10)
78/19,003
1.05 (1.00 to 1.11)
Hypertension, RR
16/4318
1.48 (1.07 to 2.06)
31/7228
1.12 (0.94 to 1.33)
Thrombocytopenia/hemorrhage, RRa
12/3714
1.17 (1.01 to 1.36)
21/4507
1.21 (1.04 to 1.42)
CI: confidence interval; FACT: Functional Assessment of Cancer Therapy; HR: hazard ratio; n/N: number of trials/number
of patients; RR: relative risk.
a Results are similar between the 2 analyses.
b No evidence of an association with erythropoiesis-stimulating agents.
c Point estimate is less than the minimal clinically important difference (3 points).
A 2014 meta-analysis examined the incidence of thromboembolic events in patients with solid and
hematologic cancers who received ESAs, and found a similar result.45 Gao et al pooled 51 RCTs
(12,115 patients) and reported a 75% increased odds of thromboembolic events among patients
receiving ESAs (pooled odds ratio, 1.75; 95% CI, 1.50 to 2.05; I2=0%).
Pegylated Epoetin Beta
PEG-epoetin beta is not FDA-approved for anemia due to cancer chemotherapy,16 and HoffmannLaRoche, manufacturer of PEG-epoetin beta, has not sought this indication.29 A 2010 phase 2, openlabel RCT by Gascon et al compared 3 doses of subcutaneous PEG-epoetin beta with subcutaneous
darbepoetin in 153 patients who were receiving first-line chemotherapy for stage 3B or 4 non-smallcell lung cancer.46 Baseline Hb at screening was 11 g/dL or less. PEG-epoetin beta was administered
every 3 weeks, and darbepoetin was administered weekly or every 3 weeks. The primary efficacy
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outcome, mean change from baseline Hb during weeks 5 to 13, did not differ between groups and
indicated inadequate treatment responses in all groups (0.17 g/dL and 0.26 g/dL in the PEG-epoetin
beta and darbepoetin groups, respectively). At week 12, the trial was terminated due to more deaths
in the 3 PEG-epoetin beta groups compared with the darbepoetin group (29 [25%] of 114 patients vs
4 [10%] of 39 patients, respectively). Post hoc analyses did not convincingly demonstrate that
baseline imbalances accounted for the mortality difference.
Section Summary
Epoetin alfa and darbepoetin alfa are approved for patients with anemia associated with concurrent
cancer chemotherapy. These ESAs effectively increase Hb concentrations and decrease the need for
blood transfusions in patients with anemia caused by cancer chemotherapy. The evidence does not
support an improvement in other clinical outcomes such as mortality, morbidity, functional status, or
QOL. Some trials have reported higher thromboembolic events and/or mortality in cancer patients
treated with ESAs, and 2 meta-analyses published in 2012 and 2013 also reported increases in
mortality and thromboembolic events. Trials that reported increased adverse events have generally
treated to a Hb of 12 g/dL or higher, and adverse events appear to be correlated with higher
treatment targets. However, it is unclear whether treating to a lower Hb reduces or eliminates these
adverse events. These concerns over potential harm from ESAs have led FDA to reassess the
risk/benefit ratio and to modify the labeled indications. Current FDA labeling recommends against
starting ESA therapy in a cancer patient whose Hb exceeds 10 g/dL.
PEG-epoetin beta is not FDA-approved for patients with anemia due to cancer chemotherapy. A
phase 2 RCT demonstrated increased mortality among patients with advanced non-small cell lung
cancer who received PEG-epoetin beta compared with those who received darbepoetin.
ESAs for Treatment of Hepatitis C-Related Anemia
Standard treatment for hepatitis C infection includes ribavirin. Anemia related to ribavirin use often
is the limiting step in treatment. Options for treatment of ribavirin-related anemia are reduction in
the dose of ribavirin and use of ESAs and/or blood transfusions as needed. However, a reduction in
ribavirin dose has been associated with less favorable response rates, and some experts therefore
prefer using ESAs to maintain full-dose ribavirin. Evidence on the benefit of using ESAs for this
purpose comprises several RCTs, some of which are reviewed next.
At least 2 RCTs randomized patients with hepatitis C and ribavirin-related anemia to epoetin alfa or
usual care. The larger of these was conducted by Afdhal et al (2004).47 This trial included 185
patients with a Hb level of 12 g/dL or less who received 8 weeks of epoetin alfa at a dose of 40,000
units weekly. Outcomes included the proportion of patients who were able to maintain full-dose
treatment with ribavirin, mean Hb level, and QOL as measured by 36-Tiem Short-Form Health
Survey. More patients in the epo group (88%) than in the usual care group (60%, p<0.001) were able
to maintain full-dose ribavirin. Increase in mean Hb level also was higher in the epo group (2.2
g/dL) than in the usual care group (0.1 g/dL, p<0.001). Improvement in QOL was significantly
greater for the epo group on 7 of 8 domains, with incremental improvement ranging from 1.3 to 10.0
for patients on epoetin.
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A second RCT by Dieterich et al (2003) was similar to the Afdhal trial.48 Dieterich et al enrolled 64
patients with hepatitis C and ribavirin-related anemia, as defined by Hb less than 12 g/dL. Patients
were followed for 16 weeks and treated with epoetin alfa 40,000 units weekly. Primary end points
were ribavirin dose and Hb level. Mean ribavirin dose decreased less in the epoetin group (-34 mg/d)
than in the usual care group (-146 mg/d), but this difference was not statistically significant (p=0.06).
More patients in the epo group (83%) than in the usual care group (54%, p=0.02) were able to
maintain full-dose ribavirin. Mean Hb level was higher in the epo group (13.8 g/dL) than in the usual
care group (11.4 g/dL, p<0.001).
A third RCT by Shiffman et al (2007) evaluated ESAs for anemia in patients with hepatitis C who
were treated with ribavirin.49 This trial randomized 150 patients to 3 groups at the onset of treatment:
(1) ribavirin at standard dose; (2) ribavirin at standard dose plus epoetin alfa; and (3) ribavirin at
higher dose plus epoetin alfa. Primary end points were reduction in ribavirin dose and the proportion
of patients with a sustained virologic response (SVR). Fewer patients treated with epoetin required
dose reduction (10%) compared with patients not treated with epo (40%, p<0.05), but the proportion
of patients with SVR did not differ between groups.
Section Summary
RCTs of ESAs versus placebo for patients with hepatitis C and ribavirin-related anemia have
demonstrated that use of ESAs can improve Hb levels and allow more patients to maintain treatment
at full ribavirin doses. One RCT also reported improvement in QOL for patients treated with ESAs.
Improvements in these parameters may lead to health outcome benefits, although no study has
reported an improvement in clinical outcomes such as SVR or survival.
Postapproval FDA Regulatory Actions
In November 2006, FDA issued a Public Health Advisory regarding the serious cardiovascular risks
from ESA therapy in patients with CKD evidenced in the CHOIR study and the NHCT study.50
Subsequently, FDA received reports of increased risks associated with ESAs used to treat anemia in
cancer patients who were receiving or not receiving chemotherapy, as well as a report of thrombotic
risks in patients receiving ESAs in the perisurgical setting. These data prompted reassessment of the
safety information contained in the Aranesp®, Epogen®, and Procrit® labels and culminated in the
approval of revised labels on March 9, 2007. Product labels have been revised and updated
subsequently, most recently in December 2013.50
Regarding dosage information, periodic reassessment of ESA safety has determined that clinical data
do not support a therapeutic Hb target free of risk for mortality. Consequently, revised “Dosage and
Administration” sections of the product label deleted any specific therapeutic Hb or Hct "target"
range for ESAs. Instead, revised labels recommended that prescribers use the lowest ESA dose that
will gradually increase Hb concentration to the lowest level sufficient to avoid the need for RBC
transfusion. For anemic CRF patients, this recommendation was primarily based on the NHCT and
CHOIR study findings, as well as the lack of data for any specific Hb or Hct threshold or range.
Clinical data did not identify specific Hb or Hct levels that directly correlated with a "reduction in
the need for red blood cell transfusion," the main treatment benefit supporting ESA efficacy. The
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March 2007 label revision allowed prescribers to use their clinical judgment in determining the
"lowest level sufficient to avoid the need for red blood cell transfusion."
On November 8, 2007, FDA revised the product labeling for epoetin alfa and darbepoetin alfa.11
These revisions clarified the evidence for safety and effectiveness of these products and provided
more explicit directions and recommendations for their use. These recommendations were consistent
with those made during the May 10, 2007 ODAC and the September 11, 2007 CRDAC and
DSRMAC meetings. Revisions included strengthened boxed warnings and “Warnings and
Precautions” sections, and changes to the “Indications and Usage,” “Clinical Trials Experience”, and
“Dosage and Administration” sections of the product labels. Product labels for Epogen®/Procrit®
and Aranesp® have been revised many times since then. The revised black box warnings and
limitations of use shown next reflect current labeling for these ESAs.13-15 Although the Mircera®
product label has not been updated since 2007, “Warnings” for use in CRF are similar to those listed
next.16
Cancer






ESAs shortened overall survival and/or increased the risk of tumor progression or
recurrence in clinical studies of patients with breast, non-small-cell lung, head, and neck,
lymphoid, and cervical cancers.
Because of these risks, prescribers and hospitals must enroll in and comply with the ESA
APPRISE Oncology Program to prescribe and/or dispense an ESA to patients with
cancer.
To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic
reactions, use the lowest dose needed to avoid RBC transfusions.
Use ESAs only for anemia from myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the
anticipated outcome is cure.
Discontinue after the completion of a chemotherapy course.
Chronic Renal Failure
 In controlled trials, patients experienced greater risks for death, serious adverse
cardiovascular reactions, and stroke when administered ESAs to target a Hb level of
greater than 11 g/dL.
 No trial has identified a Hb target level, ESA dose, or dosing strategy that does not
increase these risks.
 Use the lowest Epogen®/Procrit® or Aranesp® dose sufficient to reduce the need for
RBC transfusions.
Perisurgery (Epogen®/Procrit® only)
Due to increased risk of deep venous thrombosis (DVT), DVT prophylaxis is recommended.
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Limitations of Use
Epogen®/Procrit® and Aranesp® have not been shown to improve QOL, fatigue, or patient wellbeing (for any indication).
Epogen®/Procrit® and Aranesp® are not indicated for use:



In patients with cancer receiving hormonal agents, biologic products, or radiotherapy,
unless also receiving concomitant myelosuppressive chemotherapy.
In patients with cancer receiving myelosuppressive chemotherapy when the anticipated
outcome is cure.
As a substitute for RBC transfusions in patients who require immediate correction of
anemia
Epogen®/Procrit® also is not indicated for use:


In patients scheduled for surgery who are willing to donate autologous blood.
In patients undergoing cardiac or vascular surgery.
On February 23, 2013, FDA announced a voluntary recall of all lots of peginesatide (Omontys®)
due to postmarketing reports of serious hypersensitivity reactions, including anaphylaxis.
Peginesatide is currently discontinued.
Clinical Input Received Through Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with
and make recommendations during this process through the provision of appropriate reviewers, input
received does not represent an endorsement or position statement by the physician specialty societies
or academic medical centers, unless otherwise noted.
Responses were received from 4 academic medical centers and 2 specialty societies in 2012.
Reviewers agreed with the current medically necessary indications. There was support among
reviewers for treatment of patients with hepatitis C and ribavirin-related anemia. For investigational
indications, reviewers agreed with the current policy statements.
Summary of Evidence
This policy is based on available clinical trial evidence, as well as on recommendations for use from
the Food and Drug Administration (FDA) and from specialty societies. Erythropoiesis-stimulating
agents (ESAs) have been used extensively in patients with anemia due to cancer chemotherapy or
renal failure. Initial trials of epoetin alfa and darbepoetin alfa established that these agents
effectively increase hemoglobin (Hb) concentrations and decrease the need for blood transfusions.
However, these agents also have been associated with increases in thromboembolic events and/or
mortality, especially when the target Hb for treatment is higher. These concerns over potential harm
from ESAs led FDA to reassess the risk/benefit ratio and to modify labeled indications.
Modifications include treating to a lower target Hb and limiting ESA use in cancer to patients
receiving myelosuppressive treatment with palliative intent whose Hb concentration is less than 10
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g/dL. These additional recommendations have led to more limitations on ESA use and enhanced
surveillance systems that are intended to closely monitor and mitigate the risk of adverse events.
Based on these factors, epoetin alfa and darbepoetin alfa may be considered medically necessary for
patients with chronic renal failure (CRF) when used under the guidelines in the policy statement.
Epoetin alfa and darbepoetin alfa may be considered medically necessary in patients on dialysis and
not on dialysis and in pediatric patients with renal disease. For patients with cancer chemotherapyassociated anemia, epoetin alfa and darbepoetin may be considered medically necessary when used
under the guidelines in the policy statement. For patients with hepatitis C and anemia related to
ribavirin treatment, epoetin and darbepoetin may be considered medically necessary as a method for
avoiding dose reduction of ribavirin.
Pegylated (PEG)-epoetin beta is a long-acting epoetin that is FDA-approved for patients with anemia
due to CRF. Evidence for this indication comprises RCTs in patients on dialysis or not on dialysis
that showed noninferiority to standard ESAs for correction or maintenance of Hb levels. Metaanalyses in dialysis patients reported no difference in overall mortality, blood transfusions, or
adverse events due to hypertension or venous access thrombosis. Based on this evidence, PEGepoetin beta may be considered medically necessary for treatment of anemia due to CRF. For
treatment of anemia due to cancer chemotherapy, 1 phase 2 trial showed increased mortality with
PEG-epoetin beta compared with darbepoetin. PEG-epoetin beta is expected to become available in
the United States soon.
SUPPLEMENTAL INFORMATION
Practice Guidelines and Position Statements
ESAs in Chronic Kidney Disease
In 2007, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative updated its
evidence-based, consensus guidelines for the treatment of anemia in chronic kidney disease.17 The
guidelines reviewed evidence for epoetin alfa, epoetin beta, and darbepoetin. Updated
recommendations included Hb target of 11 to 12 g/dL (consensus recommendation); target Hb
should not exceed 13 g/dL (guideline supported by moderately strong evidence). Guideline authors
provided no specific Hb level at which to initiate ESA therapy and emphasized that treatment
decisions should be individualized (consensus recommendation).
ESAs in Oncology
Table 4 summarizes current clinical practice guidelines published jointly by the American Society of
Clinical Oncology and the American Society of Hematology9 and from the National Comprehensive
Cancer Network, version 2.2015.51

Table 4. Summary of Current Guidelines for Treatment of Anemia in Patients with Cancer
ESAs are
indicated for:
American Society of Clinical
Oncology/American Society of Hematology
2010 Clinical Practice Guideline
 ESAs are a recommended treatment option
for patients with chemotherapy-associated
National Comprehensive Cancer Network
Guidelines, Cancer and ChemotherapyInduced Anemia (v. 2.2015)
 Based on patient preference and values,
patients undergoing palliative treatment or
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ESAs are NOT
indicated for:
ESA treatment
symptom
outcomes
REMS
Hb levels for
ESA initiation
Span of ESA
treatment
ESA dosing
modifications
Hb target
Iron
Thromboembolic
risk
anemia; RBC transfusion may also be an
option
 ESAs are also a treatment option for patients
with lower risk MDS who are not undergoing
concurrent chemotherapy
 “Although FDA label now limits the indication
for ESA use to patients receiving
chemotherapy for palliative intent . . .
determining the treatment intent requires
clinical judgment of an individual patient’s
circumstances.”
 Clinicians should consider other correctable
causes of anemia before considering ESA
therapy
 Recommends against using ESAs to treat
anemia associated with malignancy in
patients (excepting those with lower risk
MDS) who are not receiving concurrent
myelosuppressive chemotherapy
Evidence does not conclusively show that ESA
use leads to improved quality of life as can be
perceived and valued by patients;
recommends that the goal of ESA use should
be to avoid transfusions.
Notes requirement
 Recommended when Hb level has
decreased to <10 g/dL. Whether to initiate
treatment when Hb is between 10 and 12
g/dL should be determined by clinical
judgment, consideration of ESA risks and
benefits (transfusion avoidance), and patient
preferences
 Transfusion is also an option
Recommends discontinuing ESA treatment
when chemotherapy concludes, per FDA
guidelines
 Recommends ESA starting doses and dose
adjustments follow FDA guidelines, noting
that alternative doses and schedules have
not improved medical outcomes
 Refers to product label directing clinicians to
use the lowest possible ESA dose (i.e.,
minimize ESA exposure) to reach the lowest
Hb level sufficient to avoid RBC transfusions
Hb can be raised to the lowest Hb level
needed to avoid RBC transfusions. An optimal
target Hb cannot be determined from the
available evidence
Iron studies at baseline and periodically during
treatment may be valuable to minimize the
need for ESA treatment, maximize
improvement of symptoms, or determine the
reason for failure to respond
Caution is urged in the use of these agents
with patients judged to be at high risk for
thromboembolic events, and regarding ESA
myelosuppressive chemotherapy without
curative intent may be treated with ESAs
using FDA-approved
indications/dosing/dosing adjustments, under
REMS guidelines, with informed consent of
patient OR may be treated with RBC
transfusions per provided guidelines
 Patients with anemia due to myelosuppressive
chemotherapy should be assessed for risk of
adverse events due to anemia and need for
initial transfusion
ESA treatment is not recommended when
patients are treated with myelosuppressive
chemotherapy with curative intent
Not discussed
Notes requirement
If Hb is <11 g/dL or >2 g/dL below baseline, an
evaluation for possible causes of anemia is
suggested. If a cause is not identified, then
anemia due to myelosuppressive chemotherapy
is considered.
Physicians are advised not to administer ESAs
outside the treatment period of cancer-related
chemotherapy
Dosing and titration directions for epoetin-alfa
and darbepoetin-alfa are reproduced from FDAapproved labels; alternative dosing regimens
are provided, e.g., every 2 or 3 wk instead of
weekly injections
No Hb target is mentioned; notes that the risks
of shortened survival and tumor progression
have not been excluded when ESAs are dosed
to a target Hb <12 g/dL
Iron studies and supplementation of functional
iron deficiency are recommended for patients
treated with ESAs
Patients with previous risk factors for
thrombosis may be at higher risk when
administered ESAs and should undergo risk
Page 20
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
use together with therapies that increase risk
assessment; the risk of ESA-associated
of thromboembolic events
thrombosis is independent of Hb levels
Response to
If a patient does not respond to ESAs after 6-8 ESA therapy should be discontinued if a patient
treatment
wk, despite a dose increase, ESA therapy
shows no response despite iron
should be discontinued and the clinician
supplementation after 8-9 wk of treatment
should investigate possible underlying tumor
progression, iron deficiency, or other causes of
the anemia
ESA: erythrocyte stimulating agent; FDA: U.S. Food and Drug Administration; Hb: hemoglobin; MDS: myelodysplastic
syndrome; RBC: red blood cell; REMS: risk evaluation and mitigation strategy.
U.S. Preventive Services Task Force Recommendations
Erythropoiesis stimulating agents for the treatment of anemia due to chronic kidney disease, cancer
chemotherapy, or ribavirin treatment of hepatitis C infection is not a preventive service.
Medicare National Coverage
In July 2007, Centers for Medicare and Medicaid Services (CMS) released a Decision Memorandum
on the use of ESAs for nonrenal disease indications (CAG-00383N).10 Safety concerns such as
thrombosis, cardiovascular events, tumor progression, and reduced survival, derived from clinical
trials in several cancer and noncancer populations, prompted CMS to review its coverage of ESAs.
CMS reviewed a large volume of scientific literature, including basic science research, to see if
safety findings observed in RCTs could be reasonably explained in whole or in part by the actions of
ESAs on normal or cancerous cells. Based on this review, CMS proposed conditions of coverage
based on expression of erythropoietin receptors. However, the scientific understanding of this
mechanism is controversial and requires additional study.
CMS also reviewed comments on ESAs for treatment of myelodysplastic syndrome (MDS), a
precursor of acute myeloid leukemia (AML) in many patients. CMS retains interest in these specific
issues but does not differentiate ESA coverage by the erythropoietin receptor status of the underlying
disease and has decided at this time to make no national coverage determination (NCD) on ESAs in
MDS.
CMS has determined that evidence is sufficient to conclude that ESA treatment is not reasonable and
necessary for beneficiaries with certain clinical conditions, either because of a deleterious effect of
the ESA on the underlying disease or because the underlying disease increases the risk of adverse
effects related to ESA use. These conditions include:







Any anemia in cancer or cancer treatment patients due to folate deficiency, vitamin B12
deficiency, iron deficiency, hemolysis, bleeding, or bone marrow fibrosis
Anemia associated with the treatment of acute and chronic myelogenous leukemias
(CML, AML), or erythroid cancers
Anemia of cancer not related to cancer treatment
Any anemia associated only with radiotherapy
Prophylactic use to prevent chemotherapy-induced anemia
Prophylactic use to reduce tumor hypoxia
Patients with erythropoietin-type resistance due to neutralizing antibodies
Page 21
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111

Anemia due to cancer treatment if patients have uncontrolled hypertension
CMS also determined that ESA treatment for anemia secondary to myelosuppressive anticancer
chemotherapy in solid tumors, multiple myeloma, lymphoma and lymphocytic leukemia is
reasonable and necessary under the following specified conditions only:






The hemoglobin (Hb) level immediately before initiation or maintenance of ESA
treatment is less than 10 g/dL (or the hematocrit [Hct] is <30%).
The starting dose for ESA treatment is the recommended FDA-labelled starting dose (no
more than 150 U/kg 3 times weekly for epoetin alfa and 2.25 mcg/kg weekly for
darbepoetin alpha). Equivalent doses may be given over other approved time periods.
Maintenance of ESA therapy is the starting dose if the Hb level remains below 10 g/dL
(or Hct is <30%) 4 weeks after initiation of therapy and the increase in Hb is greater than
1 g/dL (Hct >3%).
For patients whose Hb increases less than 1 g/dL (Hct <3%) compared with pretreatment
baseline over 4 weeks of treatment and whose Hb level remains less than 10 g/dL after 4
weeks of treatment (or Hct is <30%), the recommended FDA-labelled starting dose may
be increased once by 25%. Continued use of the drug is not reasonable and necessary if
Hb increases less than 1 g/dL (Hct <3%) compared with pretreatment baseline after 8
weeks of treatment.
Continued administration of the drug is not reasonable and necessary if there is a rapid
rise in Hb greater than 1 g/dL (Hct >3%) over 2 weeks of treatment unless Hb remains
below or subsequently falls to less than 10 g/dL (Hct <30%). Continuation and
reinstitution of ESA therapy must include a dose reduction of 25% from the previously
administered dose.
ESA treatment duration for each course of chemotherapy includes the 8 weeks after the
last dose of myelosuppressive chemotherapy in a chemotherapy regimen.
PEG-epoetin beta is not addressed in the Decision Memorandum or NCD.52
This decision by CMS allows local Medicare contractors to continue to make reasonable and
necessary determinations on all uses of ESAs that are not determined by NCD.
V. DEFINITIONS
TOP
ALLOGENEIC refers to having a different genetic constitution but belonging to the same species,
i.e., involves a donor and a recipient.
FERRITIN is an iron storage protein found in the liver, spleen and bone marrow.
HEMATOPOIESIS refers to the production and development of blood cells.
Page 22
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
IATROGENIC refers to any adverse mental or physical condition induced in a patient through the
effects of treatment.
MYELODYSPLASTIC SYNDROMES ARE a group of diseases in which the bone marrow does not
make enough healthy blood cells.
NONMYELOID REFERS to conditions not involving or affecting bone marrow.
TRANSFERRIN SATURATION IS the proportion of transferrin proteins that are carrying iron.
Normal range is 16%-45% in a fasting TS.
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under the
member’s contract. Benefit determinations should be based in all cases on the applicable contract
language. Medical policies do not constitute a description of benefits. A member’s individual or
group customer benefits govern which services are covered, which are excluded, and which are
subject to benefit limits and which require preauthorization. Members and providers should consult
the member’s benefit information or contact Capital for benefit information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider and
consult their benefit information to determine if the service is covered. If there is a discrepancy between this medical
policy and a member’s benefit information, the benefit information will govern. Capital considers the information
contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by the
terms of member benefit information. In addition, not all covered services are eligible for separate
reimbursement.
Page 23
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
May be considered medically necessary for adult patients with CKD on dialysis:
HCPCS
Code
J0882
J0887
J0890
Q4081
Description
Injection, darbepoetin alfa, 1 mcg (for esrd on dialysis)
Injection, epoetin beta, 1 microgram, (for ESRD on dialysis)
Injection, peginesatide, 0.1 mg (for esrd on dialysis)
Injection, epoetin alfa, 100 units (for esrd on dialysis)
ICD-10CM
Diagnosis
Code
D63.1
N18.3
N18.4
N18.5
N18.6
Description
Anemia in chronic kidney disease
Chronic kidney disease, stage 3 (moderate)
Chronic kidney disease, stage 4 (severe)
Chronic kidney disease, stage 5
End stage renal disease
*The list of covered diagnoses for Senior Blue members may differ from the above. If applicable, please refer to the Medicare NCD
or LCD for details.
Covered when medically necessary:
HCPCS
Code
J0881
J0885
ICD-10CM
Diagnosis
Code*
B18.2
B19.20
Description
Injection, darbepoetin alfa, 1 mcg (non-esrd use)
Injection, epoetin alfa, (for non-esrd use), 1000 units
Description
Chronic viral hepatitis C
Unspecified viral hepatitis C without hepatic coma
B19.21
B20
Unspecified viral hepatitis C with hepatic coma
Human immunodeficiency virus [HIV] disease
C00.0
C00.1
C00.2
C00.3
C00.4
Malignant neoplasm of external upper lip
Malignant neoplasm of external lower lip
Malignant neoplasm of external lip, unspecified
Malignant neoplasm of upper lip, inner aspect
Malignant neoplasm of lower lip, inner aspect
Page 24
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C00.5
C00.6
C00.8
C00.9
C01
C02.0
C02.1
C02.2
C02.3
C02.4
C02.8
C02.9
C03.0
C03.1
C03.9
C04.0
C04.1
C04.8
C04.9
C05.0
C05.1
C05.2
C05.8
C05.9
C06.0
C06.1
C06.2
C06.80
C06.89
C06.9
C07
C08.0
C08.1
C08.9
C09.0
Description
Malignant neoplasm of lip, unspecified, inner aspect
Malignant neoplasm of commissure of lip, unspecified
Malignant neoplasm of overlapping sites of lip
Malignant neoplasm of lip, unspecified
Malignant neoplasm of base of tongue
Malignant neoplasm of dorsal surface of tongue
Malignant neoplasm of border of tongue
Malignant neoplasm of ventral surface of tongue
Malignant neoplasm of anterior two-thirds of tongue, part unspecified
Malignant neoplasm of lingual tonsil
Malignant neoplasm of overlapping sites of tongue
Malignant neoplasm of tongue, unspecified
Malignant neoplasm of upper gum
Malignant neoplasm of lower gum
Malignant neoplasm of gum, unspecified
Malignant neoplasm of anterior floor of mouth
Malignant neoplasm of lateral floor of mouth
Malignant neoplasm of overlapping sites of floor of mouth
Malignant neoplasm of floor of mouth, unspecified
Malignant neoplasm of hard palate
Malignant neoplasm of soft palate
Malignant neoplasm of uvula
Malignant neoplasm of overlapping sites of palate
Malignant neoplasm of palate, unspecified
Malignant neoplasm of cheek mucosa
Malignant neoplasm of vestibule of mouth
Malignant neoplasm of retromolar area
Malignant neoplasm of overlapping sites of unspecified parts of mouth
Malignant neoplasm of overlapping sites of other parts of mouth
Malignant neoplasm of mouth, unspecified
Malignant neoplasm of parotid gland
Malignant neoplasm of submandibular gland
Malignant neoplasm of sublingual gland
Malignant neoplasm of major salivary gland, unspecified
Malignant neoplasm of tonsillar fossa
Page 25
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C09.1
C09.8
C09.9
C10.0
C10.1
C10.2
C10.3
C10.4
C10.8
C10.9
C11.0
C11.1
C11.2
C11.3
C11.8
C11.9
C12
C13.0
C13.1
C13.2
C13.8
C13.9
C14.0
C14.2
C14.8
C15.3
C15.4
C15.5
C15.8
C15.9
C16.0
C16.1
C16.2
C16.3
C16.4
Description
Malignant neoplasm of tonsillar pillar (anterior) (posterior)
Malignant neoplasm of overlapping sites of tonsil
Malignant neoplasm of tonsil, unspecified
Malignant neoplasm of vallecula
Malignant neoplasm of anterior surface of epiglottis
Malignant neoplasm of lateral wall of oropharynx
Malignant neoplasm of posterior wall of oropharynx
Malignant neoplasm of branchial cleft
Malignant neoplasm of overlapping sites of oropharynx
Malignant neoplasm of oropharynx, unspecified
Malignant neoplasm of superior wall of nasopharynx
Malignant neoplasm of posterior wall of nasopharynx
Malignant neoplasm of lateral wall of nasopharynx
Malignant neoplasm of anterior wall of nasopharynx
Malignant neoplasm of overlapping sites of nasopharynx
Malignant neoplasm of nasopharynx, unspecified
Malignant neoplasm of pyriform sinus
Malignant neoplasm of postcricoid region
Malignant neoplasm of aryepiglottic fold, hypopharyngeal aspect
Malignant neoplasm of posterior wall of hypopharynx
Malignant neoplasm of overlapping sites of hypopharynx
Malignant neoplasm of hypopharynx, unspecified
Malignant neoplasm of pharynx, unspecified
Malignant neoplasm of Waldeyer's ring
Malignant neoplasm of overlapping sites of lip, oral cavity and pharynx
Malignant neoplasm of upper third of esophagus
Malignant neoplasm of middle third of esophagus
Malignant neoplasm of lower third of esophagus
Malignant neoplasm of overlapping sites of esophagus
Malignant neoplasm of esophagus, unspecified
Malignant neoplasm of cardia
Malignant neoplasm of fundus of stomach
Malignant neoplasm of body of stomach
Malignant neoplasm of pyloric antrum
Malignant neoplasm of pylorus
Page 26
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C16.5
C16.6
C16.8
C16.9
C17.0
C17.1
C17.2
C17.3
C17.8
C17.9
C18.0
C18.1
C18.2
C18.3
C18.4
C18.5
C18.6
C18.7
C18.8
C18.9
C19
C20
C21.0
C21.1
C21.2
C21.8
C22.0
C22.1
C22.2
C22.3
C22.4
C22.7
C22.8
C22.9
C23
Description
Malignant neoplasm of lesser curvature of stomach, unspecified
Malignant neoplasm of greater curvature of stomach, unspecified
Malignant neoplasm of overlapping sites of stomach
Malignant neoplasm of stomach, unspecified
Malignant neoplasm of duodenum
Malignant neoplasm of jejunum
Malignant neoplasm of ileum
Meckel's diverticulum, malignant
Malignant neoplasm of overlapping sites of small intestine
Malignant neoplasm of small intestine, unspecified
Malignant neoplasm of cecum
Malignant neoplasm of appendix
Malignant neoplasm of ascending colon
Malignant neoplasm of hepatic flexure
Malignant neoplasm of transverse colon
Malignant neoplasm of splenic flexure
Malignant neoplasm of descending colon
Malignant neoplasm of sigmoid colon
Malignant neoplasm of overlapping sites of colon
Malignant neoplasm of colon, unspecified
Malignant neoplasm of rectosigmoid junction
Malignant neoplasm of rectum
Malignant neoplasm of anus, unspecified
Malignant neoplasm of anal canal
Malignant neoplasm of cloacogenic zone
Malignant neoplasm of overlapping sites of rectum, anus and anal canal
Liver cell carcinoma
Intrahepatic bile duct carcinoma
Hepatoblastoma
Angiosarcoma of liver
Other sarcomas of liver
Other specified carcinomas of liver
Malignant neoplasm of liver, primary, unspecified as to type
Malignant neoplasm of liver, not specified as primary or secondary
Malignant neoplasm of gallbladder
Page 27
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C24.0
C24.1
C24.8
C24.9
C25.0
C25.1
C25.2
C25.3
C25.4
C25.7
C25.8
C25.9
C26.0
C26.1
C26.9
C30.0
C30.1
C31.0
C31.1
C31.2
C31.3
C31.8
C31.9
C32.0
C32.1
C32.2
C32.3
C32.8
C32.9
C33
C34.00
C34.01
C34.02
C34.10
C34.11
Description
Malignant neoplasm of extrahepatic bile duct
Malignant neoplasm of ampulla of Vater
Malignant neoplasm of overlapping sites of biliary tract
Malignant neoplasm of biliary tract, unspecified
Malignant neoplasm of head of pancreas
Malignant neoplasm of body of pancreas
Malignant neoplasm of tail of pancreas
Malignant neoplasm of pancreatic duct
Malignant neoplasm of endocrine pancreas
Malignant neoplasm of other parts of pancreas
Malignant neoplasm of overlapping sites of pancreas
Malignant neoplasm of pancreas, unspecified
Malignant neoplasm of intestinal tract, part unspecified
Malignant neoplasm of spleen
Malignant neoplasm of ill-defined sites within the digestive system
Malignant neoplasm of nasal cavity
Malignant neoplasm of middle ear
Malignant neoplasm of maxillary sinus
Malignant neoplasm of ethmoidal sinus
Malignant neoplasm of frontal sinus
Malignant neoplasm of sphenoid sinus
Malignant neoplasm of overlapping sites of accessory sinuses
Malignant neoplasm of accessory sinus, unspecified
Malignant neoplasm of glottis
Malignant neoplasm of supraglottis
Malignant neoplasm of subglottis
Malignant neoplasm of laryngeal cartilage
Malignant neoplasm of overlapping sites of larynx
Malignant neoplasm of larynx, unspecified
Malignant neoplasm of trachea
Malignant neoplasm of unspecified main bronchus
Malignant neoplasm of right main bronchus
Malignant neoplasm of left main bronchus
Malignant neoplasm of upper lobe, unspecified bronchus or lung
Malignant neoplasm of upper lobe, right bronchus or lung
Page 28
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C34.12
C34.2
C34.30
C34.31
C34.32
C34.80
C34.81
C34.82
C34.90
C34.91
C34.92
C37
C38.0
C38.1
C38.2
C38.3
C38.4
C38.8
C39.0
C39.9
C40.00
C40.01
C40.02
C40.10
C40.11
C40.12
C40.20
C40.21
C40.22
C40.30
C40.31
C40.32
C40.80
C40.81
C40.82
Description
Malignant neoplasm of upper lobe, left bronchus or lung
Malignant neoplasm of middle lobe, bronchus or lung
Malignant neoplasm of lower lobe, unspecified bronchus or lung
Malignant neoplasm of lower lobe, right bronchus or lung
Malignant neoplasm of lower lobe, left bronchus or lung
Malignant neoplasm of overlapping sites of unspecified bronchus and lung
Malignant neoplasm of overlapping sites of right bronchus and lung
Malignant neoplasm of overlapping sites of left bronchus and lung
Malignant neoplasm of unspecified part of unspecified bronchus or lung
Malignant neoplasm of unspecified part of right bronchus or lung
Malignant neoplasm of unspecified part of left bronchus or lung
Malignant neoplasm of thymus
Malignant neoplasm of heart
Malignant neoplasm of anterior mediastinum
Malignant neoplasm of posterior mediastinum
Malignant neoplasm of mediastinum, part unspecified
Malignant neoplasm of pleura
Malignant neoplasm of overlapping sites of heart, mediastinum and pleura
Malignant neoplasm of upper respiratory tract, part unspecified
Malignant neoplasm of lower respiratory tract, part unspecified
Malignant neoplasm of scapula and long bones of unspecified upper limb
Malignant neoplasm of scapula and long bones of right upper limb
Malignant neoplasm of scapula and long bones of left upper limb
Malignant neoplasm of short bones of unspecified upper limb
Malignant neoplasm of short bones of right upper limb
Malignant neoplasm of short bones of left upper limb
Malignant neoplasm of long bones of unspecified lower limb
Malignant neoplasm of long bones of right lower limb
Malignant neoplasm of long bones of left lower limb
Malignant neoplasm of short bones of unspecified lower limb
Malignant neoplasm of short bones of right lower limb
Malignant neoplasm of short bones of left lower limb
Malignant neoplasm of overlapping sites of bone and articular cartilage of unspecified limb
Malignant neoplasm of overlapping sites of bone and articular cartilage of right limb
Malignant neoplasm of overlapping sites of bone and articular cartilage of left limb
Page 29
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C40.90
C40.91
C40.92
C41.0
C41.1
C41.2
C41.3
C41.4
C41.9
C43.0
C43.10
C43.11
C43.12
C43.20
C43.21
C43.22
C43.30
C43.31
C43.39
C43.4
C43.51
C43.52
C43.59
C43.60
C43.61
C43.62
C43.70
C43.71
C43.72
C43.8
C43.9
C44.00
C44.01
C44.02
C44.09
Description
Malignant neoplasm of unspecified bones and articular cartilage of unspecified limb
Malignant neoplasm of unspecified bones and articular cartilage of right limb
Malignant neoplasm of unspecified bones and articular cartilage of left limb
Malignant neoplasm of bones of skull and face
Malignant neoplasm of mandible
Malignant neoplasm of vertebral column
Malignant neoplasm of ribs, sternum and clavicle
Malignant neoplasm of pelvic bones, sacrum and coccyx
Malignant neoplasm of bone and articular cartilage, unspecified
Malignant melanoma of lip
Malignant melanoma of unspecified eyelid, including canthus
Malignant melanoma of right eyelid, including canthus
Malignant melanoma of left eyelid, including canthus
Malignant melanoma of unspecified ear and external auricular canal
Malignant melanoma of right ear and external auricular canal
Malignant melanoma of left ear and external auricular canal
Malignant melanoma of unspecified part of face
Malignant melanoma of nose
Malignant melanoma of other parts of face
Malignant melanoma of scalp and neck
Malignant melanoma of anal skin
Malignant melanoma of skin of breast
Malignant melanoma of other part of trunk
Malignant melanoma of unspecified upper limb, including shoulder
Malignant melanoma of right upper limb, including shoulder
Malignant melanoma of left upper limb, including shoulder
Malignant melanoma of unspecified lower limb, including hip
Malignant melanoma of right lower limb, including hip
Malignant melanoma of left lower limb, including hip
Malignant melanoma of overlapping sites of skin
Malignant melanoma of skin, unspecified
Unspecified malignant neoplasm of skin of lip
Basal cell carcinoma of skin of lip
Squamous cell carcinoma of skin of lip
Other specified malignant neoplasm of skin of lip
Page 30
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C44.101
C44.102
C44.109
C44.111
C44.112
C44.119
C44.121
C44.122
C44.129
C44.191
C44.192
C44.199
C44.201
C44.202
C44.209
C44.211
C44.212
C44.219
C44.221
C44.222
C44.229
C44.291
C44.292
C44.299
C44.300
C44.301
C44.309
C44.310
C44.311
C44.319
C44.320
C44.321
C44.329
C44.390
C44.391
Description
Unspecified malignant neoplasm of skin of unspecified eyelid, including canthus
Unspecified malignant neoplasm of skin of right eyelid, including canthus
Unspecified malignant neoplasm of skin of left eyelid, including canthus
Basal cell carcinoma of skin of unspecified eyelid, including canthus
Basal cell carcinoma of skin of right eyelid, including canthus
Basal cell carcinoma of skin of left eyelid, including canthus
Squamous cell carcinoma of skin of unspecified eyelid, including canthus
Squamous cell carcinoma of skin of right eyelid, including canthus
Squamous cell carcinoma of skin of left eyelid, including canthus
Other specified malignant neoplasm of skin of unspecified eyelid, including canthus
Other specified malignant neoplasm of skin of right eyelid, including canthus
Other specified malignant neoplasm of skin of left eyelid, including canthus
Unspecified malignant neoplasm of skin of unspecified ear and external auricular canal
Unspecified malignant neoplasm of skin of right ear and external auricular canal
Unspecified malignant neoplasm of skin of left ear and external auricular canal
Basal cell carcinoma of skin of unspecified ear and external auricular canal
Basal cell carcinoma of skin of right ear and external auricular canal
Basal cell carcinoma of skin of left ear and external auricular canal
Squamous cell carcinoma of skin of unspecified ear and external auricular canal
Squamous cell carcinoma of skin of right ear and external auricular canal
Squamous cell carcinoma of skin of left ear and external auricular canal
Other specified malignant neoplasm of skin of unspecified ear and external auricular canal
Other specified malignant neoplasm of skin of right ear and external auricular canal
Other specified malignant neoplasm of skin of left ear and external auricular canal
Unspecified malignant neoplasm of skin of unspecified part of face
Unspecified malignant neoplasm of skin of nose
Unspecified malignant neoplasm of skin of other parts of face
Basal cell carcinoma of skin of unspecified parts of face
Basal cell carcinoma of skin of nose
Basal cell carcinoma of skin of other parts of face
Squamous cell carcinoma of skin of unspecified parts of face
Squamous cell carcinoma of skin of nose
Squamous cell carcinoma of skin of other parts of face
Other specified malignant neoplasm of skin of unspecified parts of face
Other specified malignant neoplasm of skin of nose
Page 31
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C44.399
C44.40
C44.41
C44.42
C44.49
C44.500
C44.501
C44.509
C44.510
C44.511
C44.519
C44.520
C44.521
C44.529
C44.590
C44.591
C44.599
C44.601
C44.602
C44.609
C44.611
C44.612
C44.619
C44.621
C44.622
C44.629
C44.691
C44.692
C44.699
C44.701
C44.702
C44.709
C44.711
C44.712
C44.719
Description
Other specified malignant neoplasm of skin of other parts of face
Unspecified malignant neoplasm of skin of scalp and neck
Basal cell carcinoma of skin of scalp and neck
Squamous cell carcinoma of skin of scalp and neck
Other specified malignant neoplasm of skin of scalp and neck
Unspecified malignant neoplasm of anal skin
Unspecified malignant neoplasm of skin of breast
Unspecified malignant neoplasm of skin of other part of trunk
Basal cell carcinoma of anal skin
Basal cell carcinoma of skin of breast
Basal cell carcinoma of skin of other part of trunk
Squamous cell carcinoma of anal skin
Squamous cell carcinoma of skin of breast
Squamous cell carcinoma of skin of other part of trunk
Other specified malignant neoplasm of anal skin
Other specified malignant neoplasm of skin of breast
Other specified malignant neoplasm of skin of other part of trunk
Unspecified malignant neoplasm of skin of unspecified upper limb, including shoulder
Unspecified malignant neoplasm of skin of right upper limb, including shoulder
Unspecified malignant neoplasm of skin of left upper limb, including shoulder
Basal cell carcinoma of skin of unspecified upper limb, including shoulder
Basal cell carcinoma of skin of right upper limb, including shoulder
Basal cell carcinoma of skin of left upper limb, including shoulder
Squamous cell carcinoma of skin of unspecified upper limb, including shoulder
Squamous cell carcinoma of skin of right upper limb, including shoulder
Squamous cell carcinoma of skin of left upper limb, including shoulder
Other specified malignant neoplasm of skin of unspecified upper limb, including shoulder
Other specified malignant neoplasm of skin of right upper limb, including shoulder
Other specified malignant neoplasm of skin of left upper limb, including shoulder
Unspecified malignant neoplasm of skin of unspecified lower limb, including hip
Unspecified malignant neoplasm of skin of right lower limb, including hip
Unspecified malignant neoplasm of skin of left lower limb, including hip
Basal cell carcinoma of skin of unspecified lower limb, including hip
Basal cell carcinoma of skin of right lower limb, including hip
Basal cell carcinoma of skin of left lower limb, including hip
Page 32
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C44.721
C44.722
C44.729
C44.791
C44.792
C44.799
C44.80
C44.81
C44.82
C44.89
C44.90
C44.91
C44.92
C44.99
C45.0
C45.1
C45.2
C45.7
C45.9
C46.0
C46.1
C46.2
C46.3
C46.4
C46.50
C46.51
C46.52
C46.7
C46.9
C47.0
C47.10
C47.11
C47.12
C47.20
C47.21
Description
Squamous cell carcinoma of skin of unspecified lower limb, including hip
Squamous cell carcinoma of skin of right lower limb, including hip
Squamous cell carcinoma of skin of left lower limb, including hip
Other specified malignant neoplasm of skin of unspecified lower limb, including hip
Other specified malignant neoplasm of skin of right lower limb, including hip
Other specified malignant neoplasm of skin of left lower limb, including hip
Unspecified malignant neoplasm of overlapping sites of skin
Basal cell carcinoma of overlapping sites of skin
Squamous cell carcinoma of overlapping sites of skin
Other specified malignant neoplasm of overlapping sites of skin
Unspecified malignant neoplasm of skin, unspecified
Basal cell carcinoma of skin, unspecified
Squamous cell carcinoma of skin, unspecified
Other specified malignant neoplasm of skin, unspecified
Mesothelioma of pleura
Mesothelioma of peritoneum
Mesothelioma of pericardium
Mesothelioma of other sites
Mesothelioma, unspecified
Kaposi's sarcoma of skin
Kaposi's sarcoma of soft tissue
Kaposi's sarcoma of palate
Kaposi's sarcoma of lymph nodes
Kaposi's sarcoma of gastrointestinal sites
Kaposi's sarcoma of unspecified lung
Kaposi's sarcoma of right lung
Kaposi's sarcoma of left lung
Kaposi's sarcoma of other sites
Kaposi's sarcoma, unspecified
Malignant neoplasm of peripheral nerves of head, face and neck
Malignant neoplasm of peripheral nerves of unspecified upper limb, including shoulder
Malignant neoplasm of peripheral nerves of right upper limb, including shoulder
Malignant neoplasm of peripheral nerves of left upper limb, including shoulder
Malignant neoplasm of peripheral nerves of unspecified lower limb, including hip
Malignant neoplasm of peripheral nerves of right lower limb, including hip
Page 33
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C47.22
C47.3
C47.4
C47.5
C47.6
C47.8
C47.9
C48.0
C48.1
C48.2
C48.8
C49.0
C49.10
C49.11
C49.12
C49.20
C49.21
C49.22
C49.3
C49.4
C49.5
C49.6
C49.8
C49.9
C4A.0
C4A.10
C4A.11
C4A.12
C4A.20
C4A.21
C4A.22
C4A.30
C4A.31
Description
Malignant neoplasm of peripheral nerves of left lower limb, including hip
Malignant neoplasm of peripheral nerves of thorax
Malignant neoplasm of peripheral nerves of abdomen
Malignant neoplasm of peripheral nerves of pelvis
Malignant neoplasm of peripheral nerves of trunk, unspecified
Malignant neoplasm of overlapping sites of peripheral nerves and autonomic nervous
system
Malignant neoplasm of peripheral nerves and autonomic nervous system, unspecified
Malignant neoplasm of retroperitoneum
Malignant neoplasm of specified parts of peritoneum
Malignant neoplasm of peritoneum, unspecified
Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum
Malignant neoplasm of connective and soft tissue of head, face and neck
Malignant neoplasm of connective and soft tissue of unspecified upper limb, including
shoulder
Malignant neoplasm of connective and soft tissue of right upper limb, including shoulder
Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder
Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip
Malignant neoplasm of connective and soft tissue of right lower limb, including hip
Malignant neoplasm of connective and soft tissue of left lower limb, including hip
Malignant neoplasm of connective and soft tissue of thorax
Malignant neoplasm of connective and soft tissue of abdomen
Malignant neoplasm of connective and soft tissue of pelvis
Malignant neoplasm of connective and soft tissue of trunk, unspecified
Malignant neoplasm of overlapping sites of connective and soft tissue
Malignant neoplasm of connective and soft tissue, unspecified
Merkel cell carcinoma of lip
Merkel cell carcinoma of unspecified eyelid, including canthus
Merkel cell carcinoma of right eyelid, including canthus
Merkel cell carcinoma of left eyelid, including canthus
Merkel cell carcinoma of unspecified ear and external auricular canal
Merkel cell carcinoma of right ear and external auricular canal
Merkel cell carcinoma of left ear and external auricular canal
Merkel cell carcinoma of unspecified part of face
Merkel cell carcinoma of nose
Page 34
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C4A.39
C4A.4
C4A.51
C4A.52
C4A.59
C4A.60
C4A.61
C4A.62
C4A.70
C4A.71
C4A.72
C4A.8
C4A.9
C50.011
C50.012
C50.019
C50.021
C50.022
C50.029
C50.111
C50.112
C50.119
C50.121
C50.122
C50.129
C50.211
C50.212
C50.219
C50.221
C50.222
C50.229
C50.311
C50.312
C50.319
C50.321
Description
Merkel cell carcinoma of other parts of face
Merkel cell carcinoma of scalp and neck
Merkel cell carcinoma of anal skin
Merkel cell carcinoma of skin of breast
Merkel cell carcinoma of other part of trunk
Merkel cell carcinoma of unspecified upper limb, including shoulder
Merkel cell carcinoma of right upper limb, including shoulder
Merkel cell carcinoma of left upper limb, including shoulder
Merkel cell carcinoma of unspecified lower limb, including hip
Merkel cell carcinoma of right lower limb, including hip
Merkel cell carcinoma of left lower limb, including hip
Merkel cell carcinoma of overlapping sites
Merkel cell carcinoma, unspecified
Malignant neoplasm of nipple and areola, right female breast
Malignant neoplasm of nipple and areola, left female breast
Malignant neoplasm of nipple and areola, unspecified female breast
Malignant neoplasm of nipple and areola, right male breast
Malignant neoplasm of nipple and areola, left male breast
Malignant neoplasm of nipple and areola, unspecified male breast
Malignant neoplasm of central portion of right female breast
Malignant neoplasm of central portion of left female breast
Malignant neoplasm of central portion of unspecified female breast
Malignant neoplasm of central portion of right male breast
Malignant neoplasm of central portion of left male breast
Malignant neoplasm of central portion of unspecified male breast
Malignant neoplasm of upper-inner quadrant of right female breast
Malignant neoplasm of upper-inner quadrant of left female breast
Malignant neoplasm of upper-inner quadrant of unspecified female breast
Malignant neoplasm of upper-inner quadrant of right male breast
Malignant neoplasm of upper-inner quadrant of left male breast
Malignant neoplasm of upper-inner quadrant of unspecified male breast
Malignant neoplasm of lower-inner quadrant of right female breast
Malignant neoplasm of lower-inner quadrant of left female breast
Malignant neoplasm of lower-inner quadrant of unspecified female breast
Malignant neoplasm of lower-inner quadrant of right male breast
Page 35
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C50.322
C50.329
C50.411
C50.412
C50.419
C50.421
C50.422
C50.429
C50.511
C50.512
C50.519
C50.521
C50.522
C50.529
C50.611
C50.612
C50.619
C50.621
C50.622
C50.629
C50.811
C50.812
C50.819
C50.821
C50.822
C50.829
C50.911
C50.912
C50.919
C50.921
C50.922
C50.929
C51.0
C51.1
C51.2
Description
Malignant neoplasm of lower-inner quadrant of left male breast
Malignant neoplasm of lower-inner quadrant of unspecified male breast
Malignant neoplasm of upper-outer quadrant of right female breast
Malignant neoplasm of upper-outer quadrant of left female breast
Malignant neoplasm of upper-outer quadrant of unspecified female breast
Malignant neoplasm of upper-outer quadrant of right male breast
Malignant neoplasm of upper-outer quadrant of left male breast
Malignant neoplasm of upper-outer quadrant of unspecified male breast
Malignant neoplasm of lower-outer quadrant of right female breast
Malignant neoplasm of lower-outer quadrant of left female breast
Malignant neoplasm of lower-outer quadrant of unspecified female breast
Malignant neoplasm of lower-outer quadrant of right male breast
Malignant neoplasm of lower-outer quadrant of left male breast
Malignant neoplasm of lower-outer quadrant of unspecified male breast
Malignant neoplasm of axillary tail of right female breast
Malignant neoplasm of axillary tail of left female breast
Malignant neoplasm of axillary tail of unspecified female breast
Malignant neoplasm of axillary tail of right male breast
Malignant neoplasm of axillary tail of left male breast
Malignant neoplasm of axillary tail of unspecified male breast
Malignant neoplasm of overlapping sites of right female breast
Malignant neoplasm of overlapping sites of left female breast
Malignant neoplasm of overlapping sites of unspecified female breast
Malignant neoplasm of overlapping sites of right male breast
Malignant neoplasm of overlapping sites of left male breast
Malignant neoplasm of overlapping sites of unspecified male breast
Malignant neoplasm of unspecified site of right female breast
Malignant neoplasm of unspecified site of left female breast
Malignant neoplasm of unspecified site of unspecified female breast
Malignant neoplasm of unspecified site of right male breast
Malignant neoplasm of unspecified site of left male breast
Malignant neoplasm of unspecified site of unspecified male breast
Malignant neoplasm of labium majus
Malignant neoplasm of labium minus
Malignant neoplasm of clitoris
Page 36
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C51.8
C51.9
C52
C53.0
C53.1
C53.8
C53.9
C54.0
C54.1
C54.2
C54.3
C54.8
C54.9
C55
C56.1
C56.2
C56.9
C57.00
C57.01
C57.02
C57.10
C57.11
C57.12
C57.20
C57.21
C57.22
C57.3
C57.4
C57.7
C57.8
C57.9
C58
C60.0
C60.1
C60.2
Description
Malignant neoplasm of overlapping sites of vulva
Malignant neoplasm of vulva, unspecified
Malignant neoplasm of vagina
Malignant neoplasm of endocervix
Malignant neoplasm of exocervix
Malignant neoplasm of overlapping sites of cervix uteri
Malignant neoplasm of cervix uteri, unspecified
Malignant neoplasm of isthmus uteri
Malignant neoplasm of endometrium
Malignant neoplasm of myometrium
Malignant neoplasm of fundus uteri
Malignant neoplasm of overlapping sites of corpus uteri
Malignant neoplasm of corpus uteri, unspecified
Malignant neoplasm of uterus, part unspecified
Malignant neoplasm of right ovary
Malignant neoplasm of left ovary
Malignant neoplasm of unspecified ovary
Malignant neoplasm of unspecified fallopian tube
Malignant neoplasm of right fallopian tube
Malignant neoplasm of left fallopian tube
Malignant neoplasm of unspecified broad ligament
Malignant neoplasm of right broad ligament
Malignant neoplasm of left broad ligament
Malignant neoplasm of unspecified round ligament
Malignant neoplasm of right round ligament
Malignant neoplasm of left round ligament
Malignant neoplasm of parametrium
Malignant neoplasm of uterine adnexa, unspecified
Malignant neoplasm of other specified female genital organs
Malignant neoplasm of overlapping sites of female genital organs
Malignant neoplasm of female genital organ, unspecified
Malignant neoplasm of placenta
Malignant neoplasm of prepuce
Malignant neoplasm of glans penis
Malignant neoplasm of body of penis
Page 37
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C60.8
C60.9
C61
C62.00
C62.01
C62.02
C62.10
C62.11
C62.12
C62.90
C62.91
C62.92
C63.00
C63.01
C63.02
C63.10
C63.11
C63.12
C63.2
C63.7
C63.8
C63.9
C64.1
C64.2
C64.9
C65.1
C65.2
C65.9
C66.1
C66.2
C66.9
C67.0
C67.1
C67.2
C67.3
Description
Malignant neoplasm of overlapping sites of penis
Malignant neoplasm of penis, unspecified
Malignant neoplasm of prostate
Malignant neoplasm of unspecified undescended testis
Malignant neoplasm of undescended right testis
Malignant neoplasm of undescended left testis
Malignant neoplasm of unspecified descended testis
Malignant neoplasm of descended right testis
Malignant neoplasm of descended left testis
Malignant neoplasm of unspecified testis, unspecified whether descended or undescended
Malignant neoplasm of right testis, unspecified whether descended or undescended
Malignant neoplasm of left testis, unspecified whether descended or undescended
Malignant neoplasm of unspecified epididymis
Malignant neoplasm of right epididymis
Malignant neoplasm of left epididymis
Malignant neoplasm of unspecified spermatic cord
Malignant neoplasm of right spermatic cord
Malignant neoplasm of left spermatic cord
Malignant neoplasm of scrotum
Malignant neoplasm of other specified male genital organs
Malignant neoplasm of overlapping sites of male genital organs
Malignant neoplasm of male genital organ, unspecified
Malignant neoplasm of right kidney, except renal pelvis
Malignant neoplasm of left kidney, except renal pelvis
Malignant neoplasm of unspecified kidney, except renal pelvis
Malignant neoplasm of right renal pelvis
Malignant neoplasm of left renal pelvis
Malignant neoplasm of unspecified renal pelvis
Malignant neoplasm of right ureter
Malignant neoplasm of left ureter
Malignant neoplasm of unspecified ureter
Malignant neoplasm of trigone of bladder
Malignant neoplasm of dome of bladder
Malignant neoplasm of lateral wall of bladder
Malignant neoplasm of anterior wall of bladder
Page 38
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C67.4
C67.5
C67.6
C67.7
C67.8
C67.9
C68.0
C68.1
C68.8
C68.9
C69.00
C69.01
C69.02
C69.10
C69.11
C69.12
C69.20
C69.21
C69.22
C69.30
C69.31
C69.32
C69.40
C69.41
C69.42
C69.50
C69.51
C69.52
C69.60
C69.61
C69.62
C69.80
C69.81
C69.82
C69.90
Description
Malignant neoplasm of posterior wall of bladder
Malignant neoplasm of bladder neck
Malignant neoplasm of ureteric orifice
Malignant neoplasm of urachus
Malignant neoplasm of overlapping sites of bladder
Malignant neoplasm of bladder, unspecified
Malignant neoplasm of urethra
Malignant neoplasm of paraurethral glands
Malignant neoplasm of overlapping sites of urinary organs
Malignant neoplasm of urinary organ, unspecified
Malignant neoplasm of unspecified conjunctiva
Malignant neoplasm of right conjunctiva
Malignant neoplasm of left conjunctiva
Malignant neoplasm of unspecified cornea
Malignant neoplasm of right cornea
Malignant neoplasm of left cornea
Malignant neoplasm of unspecified retina
Malignant neoplasm of right retina
Malignant neoplasm of left retina
Malignant neoplasm of unspecified choroid
Malignant neoplasm of right choroid
Malignant neoplasm of left choroid
Malignant neoplasm of unspecified ciliary body
Malignant neoplasm of right ciliary body
Malignant neoplasm of left ciliary body
Malignant neoplasm of unspecified lacrimal gland and duct
Malignant neoplasm of right lacrimal gland and duct
Malignant neoplasm of left lacrimal gland and duct
Malignant neoplasm of unspecified orbit
Malignant neoplasm of right orbit
Malignant neoplasm of left orbit
Malignant neoplasm of overlapping sites of unspecified eye and adnexa
Malignant neoplasm of overlapping sites of right eye and adnexa
Malignant neoplasm of overlapping sites of left eye and adnexa
Malignant neoplasm of unspecified site of unspecified eye
Page 39
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C69.91
C69.92
C70.0
C70.1
C70.9
C71.0
C71.1
C71.2
C71.3
C71.4
C71.5
C71.6
C71.7
C71.8
C71.9
C72.0
C72.1
C72.20
C72.21
C72.22
C72.30
C72.31
C72.32
C72.40
C72.41
C72.42
C72.50
C72.59
C72.9
C73
C74.00
C74.01
C74.02
C74.10
C74.11
Description
Malignant neoplasm of unspecified site of right eye
Malignant neoplasm of unspecified site of left eye
Malignant neoplasm of cerebral meninges
Malignant neoplasm of spinal meninges
Malignant neoplasm of meninges, unspecified
Malignant neoplasm of cerebrum, except lobes and ventricles
Malignant neoplasm of frontal lobe
Malignant neoplasm of temporal lobe
Malignant neoplasm of parietal lobe
Malignant neoplasm of occipital lobe
Malignant neoplasm of cerebral ventricle
Malignant neoplasm of cerebellum
Malignant neoplasm of brain stem
Malignant neoplasm of overlapping sites of brain
Malignant neoplasm of brain, unspecified
Malignant neoplasm of spinal cord
Malignant neoplasm of cauda equina
Malignant neoplasm of unspecified olfactory nerve
Malignant neoplasm of right olfactory nerve
Malignant neoplasm of left olfactory nerve
Malignant neoplasm of unspecified optic nerve
Malignant neoplasm of right optic nerve
Malignant neoplasm of left optic nerve
Malignant neoplasm of unspecified acoustic nerve
Malignant neoplasm of right acoustic nerve
Malignant neoplasm of left acoustic nerve
Malignant neoplasm of unspecified cranial nerve
Malignant neoplasm of other cranial nerves
Malignant neoplasm of central nervous system, unspecified
Malignant neoplasm of thyroid gland
Malignant neoplasm of cortex of unspecified adrenal gland
Malignant neoplasm of cortex of right adrenal gland
Malignant neoplasm of cortex of left adrenal gland
Malignant neoplasm of medulla of unspecified adrenal gland
Malignant neoplasm of medulla of right adrenal gland
Page 40
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C74.12
C74.90
C74.91
C74.92
C75.0
C75.1
C75.2
C75.3
C75.4
C75.5
C75.8
C75.9
C76.0
C76.1
C76.2
C76.3
C76.40
C76.41
C76.42
C76.50
C76.51
C76.52
C76.8
C77.0
C77.1
C77.2
C77.3
C77.4
C77.5
C77.8
C77.9
C78.00
C78.01
C78.02
C78.1
Description
Malignant neoplasm of medulla of left adrenal gland
Malignant neoplasm of unspecified part of unspecified adrenal gland
Malignant neoplasm of unspecified part of right adrenal gland
Malignant neoplasm of unspecified part of left adrenal gland
Malignant neoplasm of parathyroid gland
Malignant neoplasm of pituitary gland
Malignant neoplasm of craniopharyngeal duct
Malignant neoplasm of pineal gland
Malignant neoplasm of carotid body
Malignant neoplasm of aortic body and other paraganglia
Malignant neoplasm with pluriglandular involvement, unspecified
Malignant neoplasm of endocrine gland, unspecified
Malignant neoplasm of head, face and neck
Malignant neoplasm of thorax
Malignant neoplasm of abdomen
Malignant neoplasm of pelvis
Malignant neoplasm of unspecified upper limb
Malignant neoplasm of right upper limb
Malignant neoplasm of left upper limb
Malignant neoplasm of unspecified lower limb
Malignant neoplasm of right lower limb
Malignant neoplasm of left lower limb
Malignant neoplasm of other specified ill-defined sites
Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck
Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes
Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes
Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes
Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes
Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes
Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions
Secondary and unspecified malignant neoplasm of lymph node, unspecified
Secondary malignant neoplasm of unspecified lung
Secondary malignant neoplasm of right lung
Secondary malignant neoplasm of left lung
Secondary malignant neoplasm of mediastinum
Page 41
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C78.2
C78.30
C78.39
C78.4
C78.5
C78.6
C78.7
C78.80
C78.89
C79.00
C79.01
C79.02
C79.10
C79.11
C79.19
C79.2
C79.31
C79.32
C79.40
C79.49
C79.51
C79.52
C79.60
C79.61
C79.62
C79.70
C79.71
C79.72
C79.81
C79.82
C79.89
C79.9
C7A.00
C7A.010
C7A.011
Description
Secondary malignant neoplasm of pleura
Secondary malignant neoplasm of unspecified respiratory organ
Secondary malignant neoplasm of other respiratory organs
Secondary malignant neoplasm of small intestine
Secondary malignant neoplasm of large intestine and rectum
Secondary malignant neoplasm of retroperitoneum and peritoneum
Secondary malignant neoplasm of liver and intrahepatic bile duct
Secondary malignant neoplasm of unspecified digestive organ
Secondary malignant neoplasm of other digestive organs
Secondary malignant neoplasm of unspecified kidney and renal pelvis
Secondary malignant neoplasm of right kidney and renal pelvis
Secondary malignant neoplasm of left kidney and renal pelvis
Secondary malignant neoplasm of unspecified urinary organs
Secondary malignant neoplasm of bladder
Secondary malignant neoplasm of other urinary organs
Secondary malignant neoplasm of skin
Secondary malignant neoplasm of brain
Secondary malignant neoplasm of cerebral meninges
Secondary malignant neoplasm of unspecified part of nervous system
Secondary malignant neoplasm of other parts of nervous system
Secondary malignant neoplasm of bone
Secondary malignant neoplasm of bone marrow
Secondary malignant neoplasm of unspecified ovary
Secondary malignant neoplasm of right ovary
Secondary malignant neoplasm of left ovary
Secondary malignant neoplasm of unspecified adrenal gland
Secondary malignant neoplasm of right adrenal gland
Secondary malignant neoplasm of left adrenal gland
Secondary malignant neoplasm of breast
Secondary malignant neoplasm of genital organs
Secondary malignant neoplasm of other specified sites
Secondary malignant neoplasm of unspecified site
Malignant carcinoid tumor of unspecified site
Malignant carcinoid tumor of the duodenum
Malignant carcinoid tumor of the jejunum
Page 42
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C7A.012
C7A.019
C7A.020
C7A.021
C7A.022
C7A.023
C7A.024
C7A.025
C7A.026
C7A.029
C7A.090
C7A.091
C7A.092
C7A.093
C7A.094
C7A.095
C7A.096
C7A.098
C7A.1
C7A.8
C80.0
C80.1
C80.2
C81.00
C81.01
C81.02
C81.03
C81.04
C81.05
C81.06
C81.07
C81.08
C81.09
Description
Malignant carcinoid tumor of the ileum
Malignant carcinoid tumor of the small intestine, unspecified portion
Malignant carcinoid tumor of the appendix
Malignant carcinoid tumor of the cecum
Malignant carcinoid tumor of the ascending colon
Malignant carcinoid tumor of the transverse colon
Malignant carcinoid tumor of the descending colon
Malignant carcinoid tumor of the sigmoid colon
Malignant carcinoid tumor of the rectum
Malignant carcinoid tumor of the large intestine, unspecified portion
Malignant carcinoid tumor of the bronchus and lung
Malignant carcinoid tumor of the thymus
Malignant carcinoid tumor of the stomach
Malignant carcinoid tumor of the kidney
Malignant carcinoid tumor of the foregut, unspecified
Malignant carcinoid tumor of the midgut, unspecified
Malignant carcinoid tumor of the hindgut, unspecified
Malignant carcinoid tumors of other sites
Malignant poorly differentiated neuroendocrine tumors
Other malignant neuroendocrine tumors
Disseminated malignant neoplasm, unspecified
Malignant (primary) neoplasm, unspecified
Malignant neoplasm associated with transplanted organ
Nodular lymphocyte predominant Hodgkin lymphoma, unspecified site
Nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of head, face, and
neck
Nodular lymphocyte predominant Hodgkin lymphoma, intrathoracic lymph nodes
Nodular lymphocyte predominant Hodgkin lymphoma, intra-abdominal lymph nodes
Nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of axilla and upper
limb
Nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of inguinal region and
lower limb
Nodular lymphocyte predominant Hodgkin lymphoma, intrapelvic lymph nodes
Nodular lymphocyte predominant Hodgkin lymphoma, spleen
Nodular lymphocyte predominant Hodgkin lymphoma, lymph nodes of multiple sites
Nodular lymphocyte predominant Hodgkin lymphoma, extranodal and solid organ sites
Page 43
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C81.10
C81.11
C81.12
C81.13
C81.14
C81.15
C81.16
C81.17
C81.18
C81.19
C81.20
C81.21
C81.22
C81.23
C81.24
C81.25
C81.26
C81.27
C81.28
C81.29
C81.30
C81.31
C81.32
C81.33
C81.34
C81.35
C81.36
C81.37
C81.38
C81.39
C81.40
C81.41
C81.42
C81.43
C81.44
Description
Nodular sclerosis Hodgkin lymphoma, unspecified site
Nodular sclerosis Hodgkin lymphoma, lymph nodes of head, face, and neck
Nodular sclerosis Hodgkin lymphoma, intrathoracic lymph nodes
Nodular sclerosis Hodgkin lymphoma, intra-abdominal lymph nodes
Nodular sclerosis Hodgkin lymphoma, lymph nodes of axilla and upper limb
Nodular sclerosis Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
Nodular sclerosis Hodgkin lymphoma, intrapelvic lymph nodes
Nodular sclerosis Hodgkin lymphoma, spleen
Nodular sclerosis Hodgkin lymphoma, lymph nodes of multiple sites
Nodular sclerosis Hodgkin lymphoma, extranodal and solid organ sites
Mixed cellularity Hodgkin lymphoma, unspecified site
Mixed cellularity Hodgkin lymphoma, lymph nodes of head, face, and neck
Mixed cellularity Hodgkin lymphoma, intrathoracic lymph nodes
Mixed cellularity Hodgkin lymphoma, intra-abdominal lymph nodes
Mixed cellularity Hodgkin lymphoma, lymph nodes of axilla and upper limb
Mixed cellularity Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
Mixed cellularity Hodgkin lymphoma, intrapelvic lymph nodes
Mixed cellularity Hodgkin lymphoma, spleen
Mixed cellularity Hodgkin lymphoma, lymph nodes of multiple sites
Mixed cellularity Hodgkin lymphoma, extranodal and solid organ sites
Lymphocyte depleted Hodgkin lymphoma, unspecified site
Lymphocyte depleted Hodgkin lymphoma, lymph nodes of head, face, and neck
Lymphocyte depleted Hodgkin lymphoma, intrathoracic lymph nodes
Lymphocyte depleted Hodgkin lymphoma, intra-abdominal lymph nodes
Lymphocyte depleted Hodgkin lymphoma, lymph nodes of axilla and upper limb
Lymphocyte depleted Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
Lymphocyte depleted Hodgkin lymphoma, intrapelvic lymph nodes
Lymphocyte depleted Hodgkin lymphoma, spleen
Lymphocyte depleted Hodgkin lymphoma, lymph nodes of multiple sites
Lymphocyte depleted Hodgkin lymphoma, extranodal and solid organ sites
Lymphocyte-rich Hodgkin lymphoma, unspecified site
Lymphocyte-rich Hodgkin lymphoma, lymph nodes of head, face, and neck
Lymphocyte-rich Hodgkin lymphoma, intrathoracic lymph nodes
Lymphocyte-rich Hodgkin lymphoma, intra-abdominal lymph nodes
Lymphocyte-rich Hodgkin lymphoma, lymph nodes of axilla and upper limb
Page 44
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C81.45
C81.46
C81.47
C81.48
C81.49
C81.70
C81.71
C81.72
C81.73
C81.74
C81.75
C81.76
C81.77
C81.78
C81.79
C81.90
C81.91
C81.92
C81.93
C81.94
C81.95
C81.96
C81.97
C81.98
C81.99
C82.00
C82.01
C82.02
C82.03
C82.04
C82.05
C82.06
C82.07
C82.08
C82.09
Description
Lymphocyte-rich Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
Lymphocyte-rich Hodgkin lymphoma, intrapelvic lymph nodes
Lymphocyte-rich Hodgkin lymphoma, spleen
Lymphocyte-rich Hodgkin lymphoma, lymph nodes of multiple sites
Lymphocyte-rich Hodgkin lymphoma, extranodal and solid organ sites
Other Hodgkin lymphoma, unspecified site
Other Hodgkin lymphoma, lymph nodes of head, face, and neck
Other Hodgkin lymphoma, intrathoracic lymph nodes
Other Hodgkin lymphoma, intra-abdominal lymph nodes
Other Hodgkin lymphoma, lymph nodes of axilla and upper limb
Other Hodgkin lymphoma, lymph nodes of inguinal region and lower limb
Other Hodgkin lymphoma, intrapelvic lymph nodes
Other Hodgkin lymphoma, spleen
Other Hodgkin lymphoma, lymph nodes of multiple sites
Other Hodgkin lymphoma, extranodal and solid organ sites
Hodgkin lymphoma, unspecified, unspecified site
Hodgkin lymphoma, unspecified, lymph nodes of head, face, and neck
Hodgkin lymphoma, unspecified, intrathoracic lymph nodes
Hodgkin lymphoma, unspecified, intra-abdominal lymph nodes
Hodgkin lymphoma, unspecified, lymph nodes of axilla and upper limb
Hodgkin lymphoma, unspecified, lymph nodes of inguinal region and lower limb
Hodgkin lymphoma, unspecified, intrapelvic lymph nodes
Hodgkin lymphoma, unspecified, spleen
Hodgkin lymphoma, unspecified, lymph nodes of multiple sites
Hodgkin lymphoma, unspecified, extranodal and solid organ sites
Follicular lymphoma grade I, unspecified site
Follicular lymphoma grade I, lymph nodes of head, face, and neck
Follicular lymphoma grade I, intrathoracic lymph nodes
Follicular lymphoma grade I, intra-abdominal lymph nodes
Follicular lymphoma grade I, lymph nodes of axilla and upper limb
Follicular lymphoma grade I, lymph nodes of inguinal region and lower limb
Follicular lymphoma grade I, intrapelvic lymph nodes
Follicular lymphoma grade I, spleen
Follicular lymphoma grade I, lymph nodes of multiple sites
Follicular lymphoma grade I, extranodal and solid organ sites
Page 45
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C82.10
C82.11
C82.12
C82.13
C82.14
C82.15
C82.16
C82.17
C82.18
C82.19
C82.20
C82.21
C82.22
C82.23
C82.24
C82.25
C82.26
C82.27
C82.28
C82.29
C82.30
C82.31
C82.32
C82.33
C82.34
C82.35
C82.36
C82.37
C82.38
C82.39
C82.40
C82.41
C82.42
C82.43
C82.44
Description
Follicular lymphoma grade II, unspecified site
Follicular lymphoma grade II, lymph nodes of head, face, and neck
Follicular lymphoma grade II, intrathoracic lymph nodes
Follicular lymphoma grade II, intra-abdominal lymph nodes
Follicular lymphoma grade II, lymph nodes of axilla and upper limb
Follicular lymphoma grade II, lymph nodes of inguinal region and lower limb
Follicular lymphoma grade II, intrapelvic lymph nodes
Follicular lymphoma grade II, spleen
Follicular lymphoma grade II, lymph nodes of multiple sites
Follicular lymphoma grade II, extranodal and solid organ sites
Follicular lymphoma grade III, unspecified, unspecified site
Follicular lymphoma grade III, unspecified, lymph nodes of head, face, and neck
Follicular lymphoma grade III, unspecified, intrathoracic lymph nodes
Follicular lymphoma grade III, unspecified, intra-abdominal lymph nodes
Follicular lymphoma grade III, unspecified, lymph nodes of axilla and upper limb
Follicular lymphoma grade III, unspecified, lymph nodes of inguinal region and lower limb
Follicular lymphoma grade III, unspecified, intrapelvic lymph nodes
Follicular lymphoma grade III, unspecified, spleen
Follicular lymphoma grade III, unspecified, lymph nodes of multiple sites
Follicular lymphoma grade III, unspecified, extranodal and solid organ sites
Follicular lymphoma grade IIIa, unspecified site
Follicular lymphoma grade IIIa, lymph nodes of head, face, and neck
Follicular lymphoma grade IIIa, intrathoracic lymph nodes
Follicular lymphoma grade IIIa, intra-abdominal lymph nodes
Follicular lymphoma grade IIIa, lymph nodes of axilla and upper limb
Follicular lymphoma grade IIIa, lymph nodes of inguinal region and lower limb
Follicular lymphoma grade IIIa, intrapelvic lymph nodes
Follicular lymphoma grade IIIa, spleen
Follicular lymphoma grade IIIa, lymph nodes of multiple sites
Follicular lymphoma grade IIIa, extranodal and solid organ sites
Follicular lymphoma grade IIIb, unspecified site
Follicular lymphoma grade IIIb, lymph nodes of head, face, and neck
Follicular lymphoma grade IIIb, intrathoracic lymph nodes
Follicular lymphoma grade IIIb, intra-abdominal lymph nodes
Follicular lymphoma grade IIIb, lymph nodes of axilla and upper limb
Page 46
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C82.45
C82.46
C82.47
C82.48
C82.49
C82.50
C82.51
C82.52
C82.53
C82.54
C82.55
C82.56
C82.57
C82.58
C82.59
C82.60
C82.61
C82.62
C82.63
C82.64
C82.65
C82.66
C82.67
C82.68
C82.69
C82.80
C82.81
C82.82
C82.83
C82.84
C82.85
C82.86
C82.87
C82.88
C82.89
Description
Follicular lymphoma grade IIIb, lymph nodes of inguinal region and lower limb
Follicular lymphoma grade IIIb, intrapelvic lymph nodes
Follicular lymphoma grade IIIb, spleen
Follicular lymphoma grade IIIb, lymph nodes of multiple sites
Follicular lymphoma grade IIIb, extranodal and solid organ sites
Diffuse follicle center lymphoma, unspecified site
Diffuse follicle center lymphoma, lymph nodes of head, face, and neck
Diffuse follicle center lymphoma, intrathoracic lymph nodes
Diffuse follicle center lymphoma, intra-abdominal lymph nodes
Diffuse follicle center lymphoma, lymph nodes of axilla and upper limb
Diffuse follicle center lymphoma, lymph nodes of inguinal region and lower limb
Diffuse follicle center lymphoma, intrapelvic lymph nodes
Diffuse follicle center lymphoma, spleen
Diffuse follicle center lymphoma, lymph nodes of multiple sites
Diffuse follicle center lymphoma, extranodal and solid organ sites
Cutaneous follicle center lymphoma, unspecified site
Cutaneous follicle center lymphoma, lymph nodes of head, face, and neck
Cutaneous follicle center lymphoma, intrathoracic lymph nodes
Cutaneous follicle center lymphoma, intra-abdominal lymph nodes
Cutaneous follicle center lymphoma, lymph nodes of axilla and upper limb
Cutaneous follicle center lymphoma, lymph nodes of inguinal region and lower limb
Cutaneous follicle center lymphoma, intrapelvic lymph nodes
Cutaneous follicle center lymphoma, spleen
Cutaneous follicle center lymphoma, lymph nodes of multiple sites
Cutaneous follicle center lymphoma, extranodal and solid organ sites
Other types of follicular lymphoma, unspecified site
Other types of follicular lymphoma, lymph nodes of head, face, and neck
Other types of follicular lymphoma, intrathoracic lymph nodes
Other types of follicular lymphoma, intra-abdominal lymph nodes
Other types of follicular lymphoma, lymph nodes of axilla and upper limb
Other types of follicular lymphoma, lymph nodes of inguinal region and lower limb
Other types of follicular lymphoma, intrapelvic lymph nodes
Other types of follicular lymphoma, spleen
Other types of follicular lymphoma, lymph nodes of multiple sites
Other types of follicular lymphoma, extranodal and solid organ sites
Page 47
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C82.90
C82.91
C82.92
C82.93
C82.94
C82.95
C82.96
C82.97
C82.98
C82.99
C83.00
C83.01
C83.02
C83.03
C83.04
C83.05
C83.06
C83.07
C83.08
C83.09
C83.10
C83.11
C83.12
C83.13
C83.14
C83.15
C83.16
C83.17
C83.18
C83.19
C83.30
C83.31
C83.32
C83.33
C83.34
Description
Follicular lymphoma, unspecified, unspecified site
Follicular lymphoma, unspecified, lymph nodes of head, face, and neck
Follicular lymphoma, unspecified, intrathoracic lymph nodes
Follicular lymphoma, unspecified, intra-abdominal lymph nodes
Follicular lymphoma, unspecified, lymph nodes of axilla and upper limb
Follicular lymphoma, unspecified, lymph nodes of inguinal region and lower limb
Follicular lymphoma, unspecified, intrapelvic lymph nodes
Follicular lymphoma, unspecified, spleen
Follicular lymphoma, unspecified, lymph nodes of multiple sites
Follicular lymphoma, unspecified, extranodal and solid organ sites
Small cell B-cell lymphoma, unspecified site
Small cell B-cell lymphoma, lymph nodes of head, face, and neck
Small cell B-cell lymphoma, intrathoracic lymph nodes
Small cell B-cell lymphoma, intra-abdominal lymph nodes
Small cell B-cell lymphoma, lymph nodes of axilla and upper limb
Small cell B-cell lymphoma, lymph nodes of inguinal region and lower limb
Small cell B-cell lymphoma, intrapelvic lymph nodes
Small cell B-cell lymphoma, spleen
Small cell B-cell lymphoma, lymph nodes of multiple sites
Small cell B-cell lymphoma, extranodal and solid organ sites
Mantle cell lymphoma, unspecified site
Mantle cell lymphoma, lymph nodes of head, face, and neck
Mantle cell lymphoma, intrathoracic lymph nodes
Mantle cell lymphoma, intra-abdominal lymph nodes
Mantle cell lymphoma, lymph nodes of axilla and upper limb
Mantle cell lymphoma, lymph nodes of inguinal region and lower limb
Mantle cell lymphoma, intrapelvic lymph nodes
Mantle cell lymphoma, spleen
Mantle cell lymphoma, lymph nodes of multiple sites
Mantle cell lymphoma, extranodal and solid organ sites
Diffuse large B-cell lymphoma, unspecified site
Diffuse large B-cell lymphoma, lymph nodes of head, face, and neck
Diffuse large B-cell lymphoma, intrathoracic lymph nodes
Diffuse large B-cell lymphoma, intra-abdominal lymph nodes
Diffuse large B-cell lymphoma, lymph nodes of axilla and upper limb
Page 48
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C83.35
C83.36
C83.37
C83.38
C83.39
C83.50
C83.51
C83.52
C83.53
C83.54
C83.55
C83.56
C83.57
C83.58
C83.59
C83.70
C83.71
C83.72
C83.73
C83.74
C83.75
C83.76
C83.77
C83.78
C83.79
C83.80
C83.81
C83.82
C83.83
C83.84
C83.85
C83.86
C83.87
C83.88
C83.89
Description
Diffuse large B-cell lymphoma, lymph nodes of inguinal region and lower limb
Diffuse large B-cell lymphoma, intrapelvic lymph nodes
Diffuse large B-cell lymphoma, spleen
Diffuse large B-cell lymphoma, lymph nodes of multiple sites
Diffuse large B-cell lymphoma, extranodal and solid organ sites
Lymphoblastic (diffuse) lymphoma, unspecified site
Lymphoblastic (diffuse) lymphoma, lymph nodes of head, face, and neck
Lymphoblastic (diffuse) lymphoma, intrathoracic lymph nodes
Lymphoblastic (diffuse) lymphoma, intra-abdominal lymph nodes
Lymphoblastic (diffuse) lymphoma, lymph nodes of axilla and upper limb
Lymphoblastic (diffuse) lymphoma, lymph nodes of inguinal region and lower limb
Lymphoblastic (diffuse) lymphoma, intrapelvic lymph nodes
Lymphoblastic (diffuse) lymphoma, spleen
Lymphoblastic (diffuse) lymphoma, lymph nodes of multiple sites
Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites
Burkitt lymphoma, unspecified site
Burkitt lymphoma, lymph nodes of head, face, and neck
Burkitt lymphoma, intrathoracic lymph nodes
Burkitt lymphoma, intra-abdominal lymph nodes
Burkitt lymphoma, lymph nodes of axilla and upper limb
Burkitt lymphoma, lymph nodes of inguinal region and lower limb
Burkitt lymphoma, intrapelvic lymph nodes
Burkitt lymphoma, spleen
Burkitt lymphoma, lymph nodes of multiple sites
Burkitt lymphoma, extranodal and solid organ sites
Other non-follicular lymphoma, unspecified site
Other non-follicular lymphoma, lymph nodes of head, face, and neck
Other non-follicular lymphoma, intrathoracic lymph nodes
Other non-follicular lymphoma, intra-abdominal lymph nodes
Other non-follicular lymphoma, lymph nodes of axilla and upper limb
Other non-follicular lymphoma, lymph nodes of inguinal region and lower limb
Other non-follicular lymphoma, intrapelvic lymph nodes
Other non-follicular lymphoma, spleen
Other non-follicular lymphoma, lymph nodes of multiple sites
Other non-follicular lymphoma, extranodal and solid organ sites
Page 49
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C83.90
C83.91
C83.92
C83.93
C83.94
C83.95
C83.96
C83.97
C83.98
C83.99
C84.00
C84.01
C84.02
C84.03
C84.04
C84.05
C84.06
C84.07
C84.08
C84.09
C84.10
C84.11
C84.12
C84.13
C84.14
C84.15
C84.16
C84.17
C84.18
C84.19
C84.40
C84.41
C84.42
C84.43
Description
Non-follicular (diffuse) lymphoma, unspecified, unspecified site
Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of head, face, and neck
Non-follicular (diffuse) lymphoma, unspecified, intrathoracic lymph nodes
Non-follicular (diffuse) lymphoma, unspecified, intra-abdominal lymph nodes
Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of axilla and upper limb
Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of inguinal region and lower
limb
Non-follicular (diffuse) lymphoma, unspecified, intrapelvic lymph nodes
Non-follicular (diffuse) lymphoma, unspecified, spleen
Non-follicular (diffuse) lymphoma, unspecified, lymph nodes of multiple sites
Non-follicular (diffuse) lymphoma, unspecified, extranodal and solid organ sites
Mycosis fungoides, unspecified site
Mycosis fungoides, lymph nodes of head, face, and neck
Mycosis fungoides, intrathoracic lymph nodes
Mycosis fungoides, intra-abdominal lymph nodes
Mycosis fungoides, lymph nodes of axilla and upper limb
Mycosis fungoides, lymph nodes of inguinal region and lower limb
Mycosis fungoides, intrapelvic lymph nodes
Mycosis fungoides, spleen
Mycosis fungoides, lymph nodes of multiple sites
Mycosis fungoides, extranodal and solid organ sites
Sézary disease, unspecified site
Sézary disease, lymph nodes of head, face, and neck
Sézary disease, intrathoracic lymph nodes
Sézary disease, intra-abdominal lymph nodes
Sézary disease, lymph nodes of axilla and upper limb
Sézary disease, lymph nodes of inguinal region and lower limb
Sézary disease, intrapelvic lymph nodes
Sézary disease, spleen
Sézary disease, lymph nodes of multiple sites
Sézary disease, extranodal and solid organ sites
Peripheral T-cell lymphoma, not classified, unspecified site
Peripheral T-cell lymphoma, not classified, lymph nodes of head, face, and neck
Peripheral T-cell lymphoma, not classified, intrathoracic lymph nodes
Peripheral T-cell lymphoma, not classified, intra-abdominal lymph nodes
Page 50
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C84.44
C84.45
C84.46
C84.47
C84.48
C84.49
C84.60
C84.61
C84.62
C84.63
C84.64
C84.65
C84.66
C84.67
C84.68
C84.69
C84.70
C84.71
C84.72
C84.73
C84.74
C84.75
C84.76
C84.77
C84.78
C84.79
C84.90
C84.91
C84.92
C84.93
C84.94
C84.95
C84.96
Description
Peripheral T-cell lymphoma, not classified, lymph nodes of axilla and upper limb
Peripheral T-cell lymphoma, not classified, lymph nodes of inguinal region and lower limb
Peripheral T-cell lymphoma, not classified, intrapelvic lymph nodes
Peripheral T-cell lymphoma, not classified, spleen
Peripheral T-cell lymphoma, not classified, lymph nodes of multiple sites
Peripheral T-cell lymphoma, not classified, extranodal and solid organ sites
Anaplastic large cell lymphoma, ALK-positive, unspecified site
Anaplastic large cell lymphoma, ALK-positive, lymph nodes of head, face, and neck
Anaplastic large cell lymphoma, ALK-positive, intrathoracic lymph nodes
Anaplastic large cell lymphoma, ALK-positive, intra-abdominal lymph nodes
Anaplastic large cell lymphoma, ALK-positive, lymph nodes of axilla and upper limb
Anaplastic large cell lymphoma, ALK-positive, lymph nodes of inguinal region and lower
limb
Anaplastic large cell lymphoma, ALK-positive, intrapelvic lymph nodes
Anaplastic large cell lymphoma, ALK-positive, spleen
Anaplastic large cell lymphoma, ALK-positive, lymph nodes of multiple sites
Anaplastic large cell lymphoma, ALK-positive, extranodal and solid organ sites
Anaplastic large cell lymphoma, ALK-negative, unspecified site
Anaplastic large cell lymphoma, ALK-negative, lymph nodes of head, face, and neck
Anaplastic large cell lymphoma, ALK-negative, intrathoracic lymph nodes
Anaplastic large cell lymphoma, ALK-negative, intra-abdominal lymph nodes
Anaplastic large cell lymphoma, ALK-negative, lymph nodes of axilla and upper limb
Anaplastic large cell lymphoma, ALK-negative, lymph nodes of inguinal region and lower
limb
Anaplastic large cell lymphoma, ALK-negative, intrapelvic lymph nodes
Anaplastic large cell lymphoma, ALK-negative, spleen
Anaplastic large cell lymphoma, ALK-negative, lymph nodes of multiple sites
Anaplastic large cell lymphoma, ALK-negative, extranodal and solid organ sites
Mature T/NK-cell lymphomas, unspecified, unspecified site
Mature T/NK-cell lymphomas, unspecified, lymph nodes of head, face, and neck
Mature T/NK-cell lymphomas, unspecified, intrathoracic lymph nodes
Mature T/NK-cell lymphomas, unspecified, intra-abdominal lymph nodes
Mature T/NK-cell lymphomas, unspecified, lymph nodes of axilla and upper limb
Mature T/NK-cell lymphomas, unspecified, lymph nodes of inguinal region and lower limb
Mature T/NK-cell lymphomas, unspecified, intrapelvic lymph nodes
Page 51
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C84.97
C84.98
C84.99
C84.A0
C84.A1
C84.A2
C84.A3
C84.A4
C84.A5
C84.A6
C84.A7
C84.A8
C84.A9
C84.Z0
C84.Z1
C84.Z2
C84.Z3
C84.Z4
C84.Z5
C84.Z6
C84.Z7
C84.Z8
C84.Z9
C85.10
C85.11
C85.12
C85.13
C85.14
C85.15
C85.16
C85.17
C85.18
C85.19
C85.20
C85.21
Description
Mature T/NK-cell lymphomas, unspecified, spleen
Mature T/NK-cell lymphomas, unspecified, lymph nodes of multiple sites
Mature T/NK-cell lymphomas, unspecified, extranodal and solid organ sites
Cutaneous T-cell lymphoma, unspecified, unspecified site
Cutaneous T-cell lymphoma, unspecified lymph nodes of head, face, and neck
Cutaneous T-cell lymphoma, unspecified, intrathoracic lymph nodes
Cutaneous T-cell lymphoma, unspecified, intra-abdominal lymph nodes
Cutaneous T-cell lymphoma, unspecified, lymph nodes of axilla and upper limb
Cutaneous T-cell lymphoma, unspecified, lymph nodes of inguinal region and lower limb
Cutaneous T-cell lymphoma, unspecified, intrapelvic lymph nodes
Cutaneous T-cell lymphoma, unspecified, spleen
Cutaneous T-cell lymphoma, unspecified, lymph nodes of multiple sites
Cutaneous T-cell lymphoma, unspecified, extranodal and solid organ sites
Other mature T/NK-cell lymphomas, unspecified site
Other mature T/NK-cell lymphomas, lymph nodes of head, face, and neck
Other mature T/NK-cell lymphomas, intrathoracic lymph nodes
Other mature T/NK-cell lymphomas, intra-abdominal lymph nodes
Other mature T/NK-cell lymphomas, lymph nodes of axilla and upper limb
Other mature T/NK-cell lymphomas, lymph nodes of inguinal region and lower limb
Other mature T/NK-cell lymphomas, intrapelvic lymph nodes
Other mature T/NK-cell lymphomas, spleen
Other mature T/NK-cell lymphomas, lymph nodes of multiple sites
Other mature T/NK-cell lymphomas, extranodal and solid organ sites
Unspecified B-cell lymphoma, unspecified site
Unspecified B-cell lymphoma, lymph nodes of head, face, and neck
Unspecified B-cell lymphoma, intrathoracic lymph nodes
Unspecified B-cell lymphoma, intra-abdominal lymph nodes
Unspecified B-cell lymphoma, lymph nodes of axilla and upper limb
Unspecified B-cell lymphoma, lymph nodes of inguinal region and lower limb
Unspecified B-cell lymphoma, intrapelvic lymph nodes
Unspecified B-cell lymphoma, spleen
Unspecified B-cell lymphoma, lymph nodes of multiple sites
Unspecified B-cell lymphoma, extranodal and solid organ sites
Mediastinal (thymic) large B-cell lymphoma, unspecified site
Mediastinal (thymic) large B-cell lymphoma, lymph nodes of head, face, and neck
Page 52
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C85.22
C85.23
C85.24
C85.25
C85.26
C85.27
C85.28
C85.29
C85.80
C85.81
C85.82
C85.83
C85.84
C85.85
C85.86
C85.87
C85.88
C85.89
C85.90
C85.91
C85.92
C85.93
C85.94
C85.95
C85.96
C85.97
C85.98
C85.99
C86.0
C86.1
C86.2
C86.3
C86.4
Description
Mediastinal (thymic) large B-cell lymphoma, intrathoracic lymph nodes
Mediastinal (thymic) large B-cell lymphoma, intra-abdominal lymph nodes
Mediastinal (thymic) large B-cell lymphoma, lymph nodes of axilla and upper limb
Mediastinal (thymic) large B-cell lymphoma, lymph nodes of inguinal region and lower
limb
Mediastinal (thymic) large B-cell lymphoma, intrapelvic lymph nodes
Mediastinal (thymic) large B-cell lymphoma, spleen
Mediastinal (thymic) large B-cell lymphoma, lymph nodes of multiple sites
Mediastinal (thymic) large B-cell lymphoma, extranodal and solid organ sites
Other specified types of non-Hodgkin lymphoma, unspecified site
Other specified types of non-Hodgkin lymphoma, lymph nodes of head, face, and neck
Other specified types of non-Hodgkin lymphoma, intrathoracic lymph nodes
Other specified types of non-Hodgkin lymphoma, intra-abdominal lymph nodes
Other specified types of non-Hodgkin lymphoma, lymph nodes of axilla and upper limb
Other specified types of non-Hodgkin lymphoma, lymph nodes of inguinal region and
lower limb
Other specified types of non-Hodgkin lymphoma, intrapelvic lymph nodes
Other specified types of non-Hodgkin lymphoma, spleen
Other specified types of non-Hodgkin lymphoma, lymph nodes of multiple sites
Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites
Non-Hodgkin lymphoma, unspecified, unspecified site
Non-Hodgkin lymphoma, unspecified, lymph nodes of head, face, and neck
Non-Hodgkin lymphoma, unspecified, intrathoracic lymph nodes
Non-Hodgkin lymphoma, unspecified, intra-abdominal lymph nodes
Non-Hodgkin lymphoma, unspecified, lymph nodes of axilla and upper limb
Non-Hodgkin lymphoma, unspecified, lymph nodes of inguinal region and lower limb
Non-Hodgkin lymphoma, unspecified, intrapelvic lymph nodes
Non-Hodgkin lymphoma, unspecified, spleen
Non-Hodgkin lymphoma, unspecified, lymph nodes of multiple sites
Non-Hodgkin lymphoma, unspecified, extranodal and solid organ sites
Extranodal NK/T-cell lymphoma, nasal type
Hepatosplenic T-cell lymphoma
Enteropathy-type (intestinal) T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Blastic NK-cell lymphoma
Page 53
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C86.5
C86.6
C88.2
C88.3
C88.4
C88.8
C88.9
C90.00
C90.01
C90.02
C90.10
C90.11
C90.12
C90.20
C90.21
C90.22
C90.30
C90.31
C90.32
C91.00
C91.01
C91.02
C91.10
C91.11
C91.12
C91.30
C91.31
C91.32
C91.40
C91.41
C91.42
C91.50
C91.51
C91.52
Description
Angioimmunoblastic T-cell lymphoma
Primary cutaneous CD30-positive T-cell proliferations
Heavy chain disease
Immunoproliferative small intestinal disease
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue [MALTlymphoma]
Other malignant immunoproliferative diseases
Malignant immunoproliferative disease, unspecified
Multiple myeloma not having achieved remission
Multiple myeloma in remission
Multiple myeloma in relapse
Plasma cell leukemia not having achieved remission
Plasma cell leukemia in remission
Plasma cell leukemia in relapse
Extramedullary plasmacytoma not having achieved remission
Extramedullary plasmacytoma in remission
Extramedullary plasmacytoma in relapse
Solitary plasmacytoma not having achieved remission
Solitary plasmacytoma in remission
Solitary plasmacytoma in relapse
Acute lymphoblastic leukemia not having achieved remission
Acute lymphoblastic leukemia, in remission
Acute lymphoblastic leukemia, in relapse
Chronic lymphocytic leukemia of B-cell type not having achieved remission
Chronic lymphocytic leukemia of B-cell type in remission
Chronic lymphocytic leukemia of B-cell type in relapse
Prolymphocytic leukemia of B-cell type not having achieved remission
Prolymphocytic leukemia of B-cell type, in remission
Prolymphocytic leukemia of B-cell type, in relapse
Hairy cell leukemia not having achieved remission
Hairy cell leukemia, in remission
Hairy cell leukemia, in relapse
Adult T-cell lymphoma/leukemia (HTLV-1-associated) not having achieved remission
Adult T-cell lymphoma/leukemia (HTLV-1-associated), in remission
Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse
Page 54
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C91.60
C91.61
C91.62
C91.90
C91.91
C91.92
C91.A0
C91.A1
C91.A2
C91.Z0
C91.Z1
C91.Z2
C92.00
C92.01
C92.02
C92.10
C92.11
C92.12
C92.20
C92.21
C92.22
C92.30
C92.31
C92.32
C92.40
C92.41
C92.42
C92.50
C92.51
C92.52
C92.60
C92.61
C92.62
C92.90
C92.91
Description
Prolymphocytic leukemia of T-cell type not having achieved remission
Prolymphocytic leukemia of T-cell type, in remission
Prolymphocytic leukemia of T-cell type, in relapse
Lymphoid leukemia, unspecified not having achieved remission
Lymphoid leukemia, unspecified, in remission
Lymphoid leukemia, unspecified, in relapse
Mature B-cell leukemia Burkitt-type not having achieved remission
Mature B-cell leukemia Burkitt-type, in remission
Mature B-cell leukemia Burkitt-type, in relapse
Other lymphoid leukemia not having achieved remission
Other lymphoid leukemia, in remission
Other lymphoid leukemia, in relapse
Acute myeloblastic leukemia, not having achieved remission
Acute myeloblastic leukemia, in remission
Acute myeloblastic leukemia, in relapse
Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission
Chronic myeloid leukemia, BCR/ABL-positive, in remission
Chronic myeloid leukemia, BCR/ABL-positive, in relapse
Atypical chronic myeloid leukemia, BCR/ABL-negative, not having achieved remission
Atypical chronic myeloid leukemia, BCR/ABL-negative, in remission
Atypical chronic myeloid leukemia, BCR/ABL-negative, in relapse
Myeloid sarcoma, not having achieved remission
Myeloid sarcoma, in remission
Myeloid sarcoma, in relapse
Acute promyelocytic leukemia, not having achieved remission
Acute promyelocytic leukemia, in remission
Acute promyelocytic leukemia, in relapse
Acute myelomonocytic leukemia, not having achieved remission
Acute myelomonocytic leukemia, in remission
Acute myelomonocytic leukemia, in relapse
Acute myeloid leukemia with 11q23-abnormality not having achieved remission
Acute myeloid leukemia with 11q23-abnormality in remission
Acute myeloid leukemia with 11q23-abnormality in relapse
Myeloid leukemia, unspecified, not having achieved remission
Myeloid leukemia, unspecified in remission
Page 55
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C92.92
C92.A0
C92.A1
C92.A2
C92.Z0
C92.Z1
C92.Z2
C93.00
C93.01
C93.02
C93.10
C93.11
C93.12
C93.30
C93.31
C93.32
C93.90
C93.91
C93.92
C93.Z0
C93.Z1
C93.Z2
C94.00
C94.01
C94.02
C94.20
C94.21
C94.22
C94.30
C94.31
C94.32
C94.80
C94.81
C94.82
C95.00
Description
Myeloid leukemia, unspecified in relapse
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
Acute myeloid leukemia with multilineage dysplasia, in remission
Acute myeloid leukemia with multilineage dysplasia, in relapse
Other myeloid leukemia not having achieved remission
Other myeloid leukemia, in remission
Other myeloid leukemia, in relapse
Acute monoblastic/monocytic leukemia, not having achieved remission
Acute monoblastic/monocytic leukemia, in remission
Acute monoblastic/monocytic leukemia, in relapse
Chronic myelomonocytic leukemia not having achieved remission
Chronic myelomonocytic leukemia, in remission
Chronic myelomonocytic leukemia, in relapse
Juvenile myelomonocytic leukemia, not having achieved remission
Juvenile myelomonocytic leukemia, in remission
Juvenile myelomonocytic leukemia, in relapse
Monocytic leukemia, unspecified, not having achieved remission
Monocytic leukemia, unspecified in remission
Monocytic leukemia, unspecified in relapse
Other monocytic leukemia, not having achieved remission
Other monocytic leukemia, in remission
Other monocytic leukemia, in relapse
Acute erythroid leukemia, not having achieved remission
Acute erythroid leukemia, in remission
Acute erythroid leukemia, in relapse
Acute megakaryoblastic leukemia not having achieved remission
Acute megakaryoblastic leukemia, in remission
Acute megakaryoblastic leukemia, in relapse
Mast cell leukemia not having achieved remission
Mast cell leukemia, in remission
Mast cell leukemia, in relapse
Other specified leukemias not having achieved remission
Other specified leukemias, in remission
Other specified leukemias, in relapse
Acute leukemia of unspecified cell type not having achieved remission
Page 56
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
C95.01
C95.02
C95.10
C95.11
C95.12
C95.90
C95.91
C95.92
C96.0
C96.2
C96.4
C96.9
C96.A
C96.Z
D03.0
D03.10
D03.11
D03.12
D03.20
D03.21
D03.22
D03.30
D03.39
D03.4
D03.51
D03.52
D03.59
D03.60
D03.61
D03.62
D03.70
D03.71
D03.72
D03.8
D03.9
Description
Acute leukemia of unspecified cell type, in remission
Acute leukemia of unspecified cell type, in relapse
Chronic leukemia of unspecified cell type not having achieved remission
Chronic leukemia of unspecified cell type, in remission
Chronic leukemia of unspecified cell type, in relapse
Leukemia, unspecified not having achieved remission
Leukemia, unspecified, in remission
Leukemia, unspecified, in relapse
Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis
Malignant mast cell tumor
Sarcoma of dendritic cells (accessory cells)
Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified
Histiocytic sarcoma
Other specified malignant neoplasms of lymphoid, hematopoietic and related tissue
Melanoma in situ of lip
Melanoma in situ of unspecified eyelid, including canthus
Melanoma in situ of right eyelid, including canthus
Melanoma in situ of left eyelid, including canthus
Melanoma in situ of unspecified ear and external auricular canal
Melanoma in situ of right ear and external auricular canal
Melanoma in situ of left ear and external auricular canal
Melanoma in situ of unspecified part of face
Melanoma in situ of other parts of face
Melanoma in situ of scalp and neck
Melanoma in situ of anal skin
Melanoma in situ of breast (skin) (soft tissue)
Melanoma in situ of other part of trunk
Melanoma in situ of unspecified upper limb, including shoulder
Melanoma in situ of right upper limb, including shoulder
Melanoma in situ of left upper limb, including shoulder
Melanoma in situ of unspecified lower limb, including hip
Melanoma in situ of right lower limb, including hip
Melanoma in situ of left lower limb, including hip
Melanoma in situ of other sites
Melanoma in situ, unspecified
Page 57
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
ICD-10CM
Diagnosis
Code*
D45
D46.21
D46.20
D46.1
D46.0
D46.4
D46.a
D46.b
D46.22
D46.c
D46.9
D46.z
D47.1
D47.Z1
D63.0
D63.1
D63.8
D64.81
N18.1
N18.2
N18.3
N18.4
N18.5
N18.6
N18.9
N19
Z48.290
Z51.11
Z51.12
Z94.81
Z94.84
Description
Polycythemia vera
Refractory anemia with excess of blasts 1
Refractory anemia with excess of blasts, unspecified
Refractory anemia with ring sideroblasts
Refractory anemia without ring sideroblasts, so stated
Refractory anemia, unspecified
Refractory cytopenia with multilineage dysplasia
Refractory cytopenia with multilineage dysplasia and ring sideroblasts
Refractory anemia with excess of blasts 2
Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality
Myelodysplastic syndrome, unspecified
Other myelodysplastic
Chronic myeloproliferative disease
Post-transplant lymphoproliferative disorder (PTLD
Anemia in neoplastic disease
Anemia in chronic kidney disease
Anemia in other chronic diseases classified elsewhere
Anemia due to antineoplastic chemotherapy
Chronic kidney disease, stage 1
Chronic kidney disease, stage 2 (mild)
Chronic kidney disease, stage 3 (moderate)
Chronic kidney disease, stage 4 (severe)
Chronic kidney disease, stage 5
End stage renal disease
Chronic kidney disease, unspecified
Unspecified kidney failure
Encounter for aftercare following bone marrow transplant
Encounter for antineoplastic chemotherapy
Encounter for antineoplastic immunotherapy
Bone marrow transplant status
Stem cells transplant status
*The list of covered diagnoses for Senior Blue members may differ from the above. If applicable, please refer to the Medicare NCD
or LCD for details.
Page 58
MEDICAL POLICY
POLICY TITLE
ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
IX. REFERENCES
TOP
1. U.S. Food and Drug Administration. Approved Risk Evaluation and Mitigation Strategies
(REMS), page last updated: 08/01/2014
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvider
s/ucm111350.htm. Accessed . January 11, 2016.
2. U.S. Food and Drug Administration. FDA Briefing Document, May 10, 2007 Oncologic Drugs
Advisory Committee. Continuing reassessment of the risks of erythropoiesis-stimulating agents
(ESAs) administered for the treatment of anemia associated with cancer chemotherapy.
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4301b2-02-FDA.pdf. Accessed January
11, 2016.
3. Grant MD, Piper M, Bohlius J, et al. Epoetin and Darbepoetin for Managing Anemia in Patients
Undergoing Cancer Treatment: Comparative Effectiveness Update. Comparative Effectiveness
Review No. 113. (Prepared by the Blue Cross and Blue Shield Association Technology
Evaluation Center Evidence-based Practice Center under Contract No. 290-2007-10058-I.)
AHRQ Publication No. 13-EHC077-EF. Rockville, MD: Agency for Healthcare Research and
Quality; April 2013. http://effectivehealthcare.ahrq.gov/search-for-guides-reviews-andreports/?pageaction=displayproduct&productID=1480. Accessed January 11, 2016.
4. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients:
updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. May 17
2006;98(10):708-714. PMID 16705125
5. Seidenfeld J, Piper M, Bohlius J, et al. Comparative Effectiveness of Epoetin and Darbepoetin
for Managing Anemia in Patients Undergoing Cancer Treatment. Comparative Effectiveness
Review No. 3. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation
Center Evidence-based Practice Center under Contract No. 290-02-0026.) Rockville, MD:
Agency for Healthcare Research and Quality; May 2006.
http://www.ncbi.nlm.nih.gov/books/NBK42982/. Accessed January 11, 2016.
6. Bohlius J, Schmidlin K, Brillant C, et al. Erythropoietin or Darbepoetin for patients with cancer-meta-analysis based on individual patient data. Cochrane Database Syst Rev.
2009(3):CD007303. PMID 19588423
7. Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents
and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. May 2
2009;373(9674):1532-1542. PMID 19410717
8. Tonia T, Mettler A, Robert N, et al. Erythropoietin or darbepoetin for patients with cancer.
Cochrane Database Syst Rev. 2012;12:CD003407. PMID 23235597
9. Rizzo JD, Brouwers M, Hurley P, et al. American Society of Clinical Oncology/American Society
of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult
patients with cancer. J Clin Oncol. Nov 20 2010;28(33):4996-5010. PMID 20975064
10. Centers for Medicare and Medicaid Services (CMS). Decision Memo for Erythropoiesis
Stimulating Agents (ESAs) for non-renal disease indications (CAG-00383N), July 30, 2007.
http://www.cms.gov/medicare-coverage-database/details/nca-decision-
Page 59
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ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
memo.aspx?NCAId=203&ver=12&NcaName=Erythropoiesis+Stimulating+Agents+&bc=BEA
AAAAAIAAA&. Accessed January 11, 2016.
11. U.S. Food and Drug Administration. FDA Briefing Document, September 11, 2007
Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk
Management Committee. Reassessment of the risks of erythropoiesis-stimulating agents (ESAs)
administered for the treatment of anemia associated with chronic renal failure.
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4315b1-01-FDA.pdf. Accessed January
11, 2016.
12. Strippoli GF, Craig JC, Manno C, et al. Hemoglobin targets for the anemia of chronic kidney
disease: a meta-analysis of randomized, controlled trials. J Am Soc Nephrol. Dec
2004;15(12):3154-3165. PMID 15579519
13. Amgen Inc. Epogen® (epoetin alfa) injection for intravenous or subcutaneous use prescribing
information, April 2014. http://www.epogen.com/. Accessed January11, 2016..
14. Amgen Inc. Procrit® (epoetin alfa) injection for intravenous or subcutaneous use prescribing
information, December 2013. http://www.procrit.com/. Accessed January 11, 2016.
15. Amgen Inc. Aranesp® (darbepoetin alfa) injection for intravenous or subcutaneous use
prescribing information, July 2015.http://www.aranesp.com. Accessed January 11, 2016.
16. Hoffmann-La Roche, Inc. Mircera® (methoxy polyethylene glycol-epoetin beta) solution for
injection: intravenous (IV) or subcutaneous (SC) use prescribing information, November 2007.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/125164lbl.pdf. Accessed January 11,
2016.
17. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in
chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. Sep
2007;50(3):471-530. PMID 17720528
18. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit
values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J
Med. Aug 27 1998;339(9):584-590. PMID 9718377
19. Fishbane S, Besarab A. Mechanism of increased mortality risk with erythropoietin treatment to
higher hemoglobin targets. Clin J Am Soc Nephrol. Nov 2007;2(6):1274-1282. PMID 17942772
20. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney
disease. N Engl J Med. Nov 16 2006;355(20):2085-2098. PMID 17108343
21. Inrig JK, Barnhart HX, Reddan D, et al. Effect of hemoglobin target on progression of kidney
disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal
Insufficiency) trial. Am J Kidney Dis. Sep 2012;60(3):390-401. PMID 22537421
22. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with
chronic kidney disease and anemia. N Engl J Med. Nov 16 2006;355(20):2071-2084. PMID
17108342
23. Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and
chronic kidney disease. N Engl J Med. Nov 19 2009;361(21):2019-2032. PMID 19880844
24. Skali H, Parving HH, Parfrey PS, et al. Stroke in patients with type 2 diabetes mellitus, chronic
kidney disease, and anemia treated with Darbepoetin Alfa: the trial to reduce cardiovascular
events with Aranesp therapy (TREAT) experience. Circulation. Dec 20 2011;124(25):2903-2908.
PMID 22104547
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ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
25. Vinhas J, Barreto C, Assuncao J, et al. Treatment of anaemia with erythropoiesis-stimulating
agents in patients with chronic kidney disease does not lower mortality and may increase
cardiovascular risk: a meta-analysis. Nephron Clin Pract. 2012;121(3-4):c95-101. PMID
23182871
26. Williams AW, Dwyer AC, Eddy AA, et al. Critical and honest conversations: the evidence behind
the "Choosing Wisely" campaign recommendations by the American Society of Nephrology. Clin
J Am Soc Nephrol. Oct 2012;7(10):1664-1672. PMID 22977214
27. Palmer SC, Saglimbene V, Craig JC, et al. Darbepoetin for the anaemia of chronic kidney
disease. Cochrane Database Syst Rev. 2014;3:CD009297. PMID 24683046
28. Walker RG, Strippoli GF. A pegylated epoetin in anaemia of renal disease: non-inferiority for an
unvalidated surrogate. Lancet. Oct 20 2007;370(9596):1395-1396. PMID 17950848
29. U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Office Director
Memo: application number BLA 125164.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/125164TOC.cfm. Accessed AJanuary
11, 2106.
30. Macdougall IC, Walker R, Provenzano R, et al. C.E.R.A. corrects anemia in patients with
chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc
Nephrol. Mar 2008;3(2):337-347. PMID 18287255
31. Klinger M, Arias M, Vargemezis V, et al. Efficacy of intravenous methoxy polyethylene glycolepoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in
patients treated by hemodialysis or peritoneal dialysis: a randomized trial. Am J Kidney Dis.
Dec 2007;50(6):989-1000. PMID 18037099
32. Levin NW, Fishbane S, Canedo FV, et al. Intravenous methoxy polyethylene glycol-epoetin beta
for haemoglobin control in patients with chronic kidney disease who are on dialysis: a
randomised non-inferiority trial (MAXIMA). Lancet. Oct 20 2007;370(9596):1415-1421. PMID
17950856
33. Sulowicz W, Locatelli F, Ryckelynck JP, et al. Once-monthly subcutaneous C.E.R.A. maintains
stable hemoglobin control in patients with chronic kidney disease on dialysis and converted
directly from epoetin one to three times weekly. Clin J Am Soc Nephrol. Jul 2007;2(4):637-646.
PMID 17699476
34. Canaud B, Mingardi G, Braun J, et al. Intravenous C.E.R.A. maintains stable haemoglobin
levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a
randomized phase III study. Nephrol Dial Transplant. Nov 2008;23(11):3654-3661. PMID
18586762
35. Spinowitz B, Coyne DW, Lok CE, et al. C.E.R.A. maintains stable control of hemoglobin in
patients with chronic kidney disease on dialysis when administered once every two weeks. Am J
Nephrol. 2008;28(2):280-289. PMID 18004064
36. Hahn D, Cody JD, Hodson EM. Frequency of administration of erythropoiesis-stimulating
agents for the anaemia of end-stage kidney disease in dialysis patients. Cochrane Database Syst
Rev. 2014;5:CD003895. PMID 24872328
37. Oh J, Joo KW, Chin HJ, et al. Correction of anemia with continuous erythropoietin receptor
activator in Korean patients on long-term hemodialysis. J Korean Med Sci. Jan 2014;29(1):7683. PMID 24431909
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ERYTHROPOIESIS-STIMULATING AGENTS (ESAS)
POLICY NUMBER
MP-2.111
38. Vankar SG, Dutta P, Kohli HS, et al. Efficacy & safety of continuous erythropoietin receptor
activator (CERA) in treating renal anaemia in diabetic patients with chronic kidney disease not
on dialysis. Indian J Med Res. Jan 2014;139(1):112-116. PMID 24604046
39. Roger SD, Locatelli F, Woitas RP, et al. C.E.R.A. once every 4 weeks corrects anaemia and
maintains haemoglobin in patients with chronic kidney disease not on dialysis. Nephrol Dial
Transplant. Dec 2011;26(12):3980-3986. PMID 21505096
40. Al-Ali FS, El-Sayed Abdelfattah M, Fawzy AA, et al. Erythropoietin-stimulating agents in the
management of anemia of end-stage renal disease patients on regular hemodialysis: A
prospective randomized comparative study from Qatar. Hemodial Int. Jun 3 2014. PMID
24894344
41. Hirai T, Nishizawa Y, Nakazono H, et al. Hemoglobin maintenance and dosing strategies using
intravenous continuous erythropoietin receptor activator in Japanese hemodialysis patients.
Ther Apher Dial. Oct 2013;17(5):498-503. PMID 24107278
42. Kessler M, Martinez-Castelao A, Siamopoulos KC, et al. C.E.R.A. once every 4 weeks in patients
with chronic kidney disease not on dialysis: The ARCTOS extension study. Hemodial Int. Apr
2010;14(2):233-239. PMID 19888948
43. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). TEC Specialty
Pharmacy Reports 2012. Peginesatide: #6-2012.
44. U.S. Food and Drug Administration. MedWatch Safety Information and Adverse Event
Reporting. Omontys (peginesatide) Injection by Affymax and Takeda: Recall of All Lots - Serious
Hypersensitivity Reactions. February 23, 2013.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/
ucm340895.htm?source=govdelivery. Accessed January 11, 2016.
45. Gao S, Ma JJ, Lu C. Venous thromboembolism risk and erythropoiesis-stimulating agents for the
treatment of cancer-associated anemia: a meta-analysis. Tumour Biol. Jan 2014;35(1):603-613.
PMID 23959477
46. Gascon P, Pirker R, Del Mastro L, et al. Effects of CERA (continuous erythropoietin receptor
activator) in patients with advanced non-small-cell lung cancer (NSCLC) receiving
chemotherapy: results of a phase II study. Ann Oncol. Oct 2010;21(10):2029-2039. PMID
20335369
47. Afdhal NH, Dieterich DT, Pockros PJ, et al. Epoetin alfa maintains ribavirin dose in HCVinfected patients: a prospective, double-blind, randomized controlled study. Gastroenterology.
May 2004;126(5):1302-1311. PMID 15131791
48. Dieterich DT, Wasserman R, Brau N, et al. Once-weekly epoetin alfa improves anemia and
facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving
ribavirin plus interferon alfa. Am J Gastroenterol. Nov 2003;98(11):2491-2499. PMID
14638354
49. Shiffman ML, Salvatore J, Hubbard S, et al. Treatment of chronic hepatitis C virus genotype 1
with peginterferon, ribavirin, and epoetin alpha. Hepatology. Aug 2007;46(2):371-379. PMID
17559152
50. U.S. Food and Drug Administration. Postmarket Drug Safety Information for Patients and
Providers: Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as
Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp).
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http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/u
cm109375.htm. Accessed January11, 2016..
51. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology:
cancer- and chemotherapy-induced anemia, version 2.2016.
http://www.nccn.org/professionals/physician_gls/pdf/anemia.pdf. Accessed January 11, 2016.
52. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination (NCD)
for Erythropoiesis Stimulating Agents (ESAs) in Cancer and Related Neoplastic Conditions
(110.21), July 30, 2007. http://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?NCDId=322&ncdver=1&bc=AAAAgAAAAAAAAA%3d%3d&. Accessed January
11, 2016.
Other:
FDA Recall-Firm Press Release. Affymax and Takeda Announce a Nationwide Voluntary Recall of
All Lots of OMONTYS® (peginesatide) Injection February 23, 2013. [Website]:
http://www.fda.gov/Safety/Recalls/ucm340893.htm Accessed January11, 2016.
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD)
110.21. Erythropoiesis Stimulating Agents (ESAs) in Cancer and Related Neoplastic Conditions.
Effective 7/30/07. CMS [Website]: https://www.cms.gov Accessed January 11, 2016.
Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual. Publication
100-02. Chapter 15 Covered Medical and Other Services. Effective 01/14/14. [Website]:
http://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Downloads/bp102c15.pdf
Accessed January 11, 2016.
Taber's Cyclopedic Medical Dictionary, 20th edition
X. POLICY HISTORY
MP 2.111
TOP
CAC 5/25/04
CAC 11/30/04
CAC 10/25/05
CAC 9/26/06
CAC 4/24/07
CAC 7/29/08
CAC 7/28/09 Consensus Review
CAC 11/24/09 Policy revised with additional medical necessity criteria for treatment of
anemia associated with Hepatitis C medications.
CAC 9/28/10 Added “not medically necessary” indication for orthostatic hypotension.
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CAC 11/22/11 Adopted BCBSA. Retained CBC investigational indication for orthostatic
hypotension. Policy criteria for use of ESAs for autologous stem-cell support, noniatrogenic chronic anemia of cancer and orthostatic hypotension revised from not medically
necessary to investigational. FDA qualifying statement added to criteria for ESA use in
cancer conditions. Description and Background revised per BCBSA updates. FEP
variation added. Added Medicare variation for treatment of anemia related to specified
chronic diseases.
CAC 6/26/12 Minor Revision. Added recently approved (3/12) new long –acting ESA
Peginesatide (Omontys) to the policy considered medically necessary for treatment of
anemia due to chronic kidney disease in adult patients on dialysis. Also added an off label
indication for treatment of ribavirin induced anemia in patients being treated for Hepatitis
C. FEP variation revised. FEP requires prior-approval for these agents. Boxed warnings
revised to reflect current FDA-prescribing information.
2013 Codes added-12/20/2013
Admin posting 2/28/13. Information in policy related to Omontys removed from
policy due to product recall.
Admin posting 3-8-13 Prior auth requirement removed from FEP variation. Code
J0890 added
CAC 7/30/13 Minor review.
Added the following:
 Information on Omontys (peginesatice) recall to Background/Description
 Policy guidelines
 Reference to NCD 110.11 Erythropoiesis Stimulating Agnets (ESAs) in
Cancer and Related Neoplastic Conditions in the Medicare variation.
 Rationale section.
CAC 3/25/14 Consensus review. References updated. No change to policy
statements. Background information updated. LCD variation removed as policy
was retired. Variation now refers to the Centers for Medicare and Medicaid
Services (CMS) Medicare Benefit Policy Chapter 15 for coverage of ESA’s for
end-stage renal disease related anemia.
CAC 3/24/15 Minor. Information about pegylated (PEG) epoetin beta (Mircera®)
added and medically necessary policy statement updated to include PEG-epoetin
beta for treatment of anemia associated with chronic kidney disease; PEG-epoetin
beta is investigational for all other uses. Rationale and references updated. Coding
reviewed.
10/22/15 Coding updated. Added additional diagnosis codes applicable to the
policy.
CAC 3/29/16 Consensus review. No changes to the policy statements. Reference
and rationale updated. Coding reviewed.
1/1/17 Administrative-Variations reformatted. Revised code definitions updated
effective 10/1/2016
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Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company®, Capital
Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the BlueCross BlueShield Association.
Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies.
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