Download Pharmacy Medical Necessity Guidelines

Pharmacy Medical Necessity Guidelines: IclusigTM (ponatinib)
Effective: January 10, 2017
Prior Authorization Required
√
Type of Review – Care Management
Not Covered
Type of Review – Clinical Review
√
Pharmacy (RX) or Medical (MED) Benefit
RX Department to Review
RXUM
This Pharmacy Medical Necessity Guideline applies to the following:
Fax Numbers:
Tufts Health Plan Commercial Plans
Tufts Health Plan Commercial Plans – large group plans
Tufts Health Plan Commercial Plans – small group and individual plans
Tufts Health Public Plans
RXUM:
617.673.0988
Tufts Health Direct – Health Connector
Tufts Health Together – A MassHealth Plan
Tufts Health Freedom Plan products
Tufts Health Freedom Plan – large group plans
Tufts Health Freedom Plan – small group plans
Note: For Tufts Health Plan Medicare Preferred Members, please refer to the Tufts Health Plan
Medicare Preferred Prior Authorization Criteria. Background, applicable product and disclaimer
information can be found on the last page.
OVERVIEW
Chronic myeloid leukemia (CML) is a cancer of blood cells, characterized by replacement of the bone
marrow with malignant, leukemic cells. Many of these leukemic cells can be found circulating in the
blood and can cause enlargement of the spleen, liver, and other organs.
CML is usually diagnosed by finding a specific chromosomal abnormality called the Philadelphia (Ph)
chromosome. The Ph chromosome is the result of a translocation or exchange of genetic material
between the long arms of chromosomes 9 and 22. This exchange brings together two genes: the BCR
(breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia
virus) on chromosome 9. The resulting hybrid gene, BCR-ABL, codes for a fusion protein with tyrosine
kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth.
There is no standard staging system for CML. Instead, the disease is classified by phases: chronic
phase, accelerated phase, or blastic phase. As the amount of blast cells increases in the blood and
bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may
result in infections, anemia, and easy bleeding, as well as bone pain and pain or a feeling of fullness
below the ribs on the left side. The number of blast cells in the blood and bone marrow and the
severity of symptoms determine the phase of the disease. In chronic phase CML, 10% or fewer of the
cells in the blood and bone marrow are blast cells. This phase may last from several months to several
years, and there may be no symptoms of leukemia. In accelerated phase CML, the disease is
progressing and 10% to 19% of cells in the blood and bone marrow are blast cells. Once more then
20% of these cells are blast cells, the disease has progressed to blastic phase. The median age of
patients with Ph chromosome positive CML is 67 years. The median survival is 4 to 6 years, with a
range of less than 1 year to more than 10 years. Survival after development of an accelerated phase
is usually less than 1 year and after blastic transformation is only a few months.
Imatinib (Gleevec®) remains the gold standard of treatment for newly diagnosed Ph chromosome
positive CML patients. The 5-year rates of complete cytogenetic response and overall survival for
patients originally randomized to imatinib in the IRIS trial are 87% and 89%, respectively. However, a
small percentage of patients either fail to respond to imatinib or lose their response over time. And
while adverse events with imatinib are generally mild to moderate and can be managed, a small
percentage of patients discontinue imatinib therapy due to intolerable or severe side effects.
Iclusig (ponatinib) is an oral multi-kinase inhibitor indicated for the second-line treatment of CML or
Ph chromosome positive acute lymphoblastic leukemia (ALL). The agent has demonstrated efficacy in
patients resistant or intolerant to Sprycel (dasatinib) or Tasigna (nilotinib) as well as patients with the
T315I mutation in all phases of CML.
2222092
1
Pharmacy Medical Necessity Guidelines:
IclusigTM (ponatinib)
FOOD AND DRUG ADMINISTRATION-APPROVED INDICATIONS
Iclusig (ponatinib) is indicated for the treatment of adult patients with T315I-positive CML (chronic,
accelerated, or blast phase) or T315I-positive Ph chromosome positive ALL. Iclusig (ponatinib) is also
indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase
CML or Ph chromosome positive ALL for whom no other tyrosine kinase inhibitor therapy is indicated.
Iclusig (ponatinib) is not indicated and is not recommended for the treatment of patients with newly
diagnosed chronic phase CML.
COVERAGE GUIDELINES
The plan may authorize coverage of Iclusig (ponatinib) for Members, when all the following criteria are
met:
1. Documented diagnosis of T315I-positive chronic myeloid leukemia (chronic phase, accelerated
phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic
leukemia
AND
2. The prescribing physician is an oncologist
OR
3. Documented diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid
leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia
AND
4. Documentation that no other tyrosine kinase inhibitor therapy is indicated
AND
5. The prescribing physician is an oncologist
Off-label Use Coverage for Other Cancer Diagnoses
Coverage for other cancer diagnoses may be authorized provided effective treatment with such drug is
recognized for treatment of such indication in one of the standard reference compendia, or in the
medical literature, or by the Massachusetts commissioner of Insurance (commissioner) under the
provisions of the “Sullivan Law”: (M.G.L. c.175, s.47K ).
The plan may authorize coverage for use for other cancer diagnoses provided effective treatment with
such drug is recognized as a “Medically Accepted Indication” according to the National Comprehensive
Cancer Network (NCCN) Drugs and Biologics Compendium as indicated by a Category 1 or 2A for
quality of evidence and level of consensus.
Note: The plan requires prescribers to submit clinical documentation supporting the drug's
effectiveness in treating the intended malignancy, including the applicable NCCN guideline(s).
In cases where the requested off-label use for the diagnosis is not recognized by the NCCN Drugs and
Biologics Compendium, the plan will follow the Centers for Medicare and Medicaid Services (CMS)
guidance, unless otherwise directed by the commissioner, and accept clinical documentation
referenced in one of the other “Standard Reference Compendia” noted below or supported by clinical
research that appears in a regular edition of a "Peer-Reviewed Medical Literature" noted below.
"Standard Reference Compendia"
1. American Hospital Formulary Service – Drug Information (AHFS-DI)
2. Thomson Micromedex DrugDex
3. Clinical Pharmacology (Gold Standard)
4. Wolters Kluwer Lexi-Drugs
2
Pharmacy Medical Necessity Guidelines:
IclusigTM (ponatinib)
"Peer Reviewed Medical Literature"

American Journal of Medicine

Annals of Internal Medicine

Annals of Oncology

Annals of Surgical Oncology

Biology of Blood and Marrow Transplantation

Blood

Bone Marrow Transplantation

British Journal of Cancer

British Journal of Hematology

British Medical Journal

Cancer

Clinical Cancer Research

Drugs

European Journal of Cancer (formerly the
European Journal of Cancer and Clinical
Oncology)












Gynecologic Oncology
International Journal of Radiation, Oncology,
Biology, and Physics
The Journal of the American Medical
Association
Journal of Clinical Oncology
Journal of the National Cancer Institute
Journal of the National Comprehensive Cancer
Network (NCCN)
Journal of Urology
Lancet
Lancet Oncology
Leukemia
The New England Journal of Medicine
Radiation Oncology
When the plan evaluates the evidence in published, peer-reviewed medical literature, consideration
will be given to the following:
1. Whether the clinical characteristics of the beneficiary and the cancer are adequately represented in
the published evidence.
2. Whether the administered chemotherapy regimen is adequately represented in the published
evidence.
3. Whether the reported study outcomes represent clinically meaningful outcomes experienced by
patients.
4. Whether the study is appropriate to address the clinical question.
a. whether the experimental design, in light of the drugs and conditions under investigation, is
appropriate to address the investigative question (e.g., in some clinical studies, it may be
unnecessary or not feasible to use randomization, double blind trials, placebos, or crossover);
b. that non-randomized clinical trials with a significant number of subjects may be a basis for
supportive clinical evidence for determining accepted uses of drugs; and,
c. that case reports are generally considered uncontrolled and anecdotal information and do not
provide adequate supportive clinical evidence for determining accepted uses of drugs.
LIMITATIONS
1. The plan will not authorize the use of Iclusig (ponatinib) for conditions other than those listed
above without appropriate documentation.
2. The plan will limit the supply of Iclusig (ponatinib) to the following:
15 mg
45 mg
60 tablets per 30 days
30 tablets per 30 days
CODES
None
REFERENCES
1. American Cancer Society (ACS). Detailed Guide: Leukemia – Chronic Myeloid (Myelogenous). URL:
http://www.cancer.org/cancer/leukemia-chronicmyeloidcml/detailedguide/index. Available from
Internet. Accessed 2016 January 25.
2. Cortes JE, Talpaz M, O’Brien S, et al. Staging of chronic myeloid leukemia in the imatinib era: an
evaluation of the World Health Organization proposal. Cancer. 2006 Mar 15;106(6):1306-15.
3. Deininger MW, O’Brien SG, Ford JM, et al. Practical management of patients with chronic myeloid
leukemia receiving imatinib. J Clin Oncol. 2003;21:1637-1647.
4. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for
chronic myeloid leukemia. N Engl J Med. 2006;355:2408-2417.
5. Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals
Corporation; 2015 January.
6. Goldman JM. Ponatinib for chronic myeloid leukemia. N Engl J Med. 2012;367(22):2148-9.
7. Iclusig (ponatinib) [prescribing information]. Cambridge, MA: ARIAD Pharmaceuticals, Inc.,
November 2016.
3
Pharmacy Medical Necessity Guidelines:
IclusigTM (ponatinib)
8. Kantarjian H, Wunderle L, Giles F, et al. Nilotinib in imatinib-resistant CML and philadelphia
chromosome–positive ALL. N Engl J Med. 2006;354:2542-51.
9. Kantarjian HM, O’Brien S, Cortes J, et al. Therapeutic advances in leukemia and myelodysplastic
syndrome over the past 40 years. Cancer. 2008;113(7 Suppl):1933-52.
10. Lee SJ, Anasetti C, Horowitz MM, et al. Initial therapy for chronic myelogenous leukemia: playing
the odds. J Clin Oncol. 1998;16(9):2897-903.
11. National Cancer Institute. Chronic Myelogenous Leukemia Treatment-for health professionals
(PDG®). URL: http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq. Available from the
Internet. Accessed 2016 January 25.
12. National Comprehensive Cancer Network. Chronic myelogenous leukemia. 1.2016. URL:
http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Available from Internet. Accessed
2016 January 25.
13. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose
cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med.
2003;348:994-1004.
14. O’Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res.
2005;65:4500-5.
15. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340(17):1330-40.
16. Shah, NP. Loss of response to imatinib: mechanics and management. Hematology Am Soc
Hematol Educ Program. 2005;183-87.
17. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of
native and mutant Bcr-Abl. Cancer Cell. 2005;7:129-141.
18. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. PACE: a pivotal phase II trial of ponatinib in patients with
CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. J Clin
Oncol. 2012(suppl; abstr 6503).
19. Sprycel (dasatinib) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2015 August.
20. Tasigna (nilotinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals
Corporation; 2015 October.
APPROVAL HISTORY
March 12, 2013: Reviewed by Pharmacy & Therapeutics Committee.
Subsequent endorsement date(s) and changes made:

March 11, 2014: Updated criteria to be consistent with revised indications following voluntary
market withdrawal and reintroduction.

March 10, 2015: No changes

January 1, 2016: Administrative change to rebranded template.

February 9, 2016: No changes

January 10, 2017: No changes. Effective 1/10/17, Medical Necessity Guideline applies to Tufts
Health Together.
BACKGROUND, PRODUCT AND DISCLAIMER INFORMATION
Pharmacy Medical Necessity Guidelines have been developed for determining coverage for plan
benefits and are published to provide a better understanding of the basis upon which coverage
decisions are made. They are used in conjunction with a Member’s benefit document and in
coordination with the Member’s physician(s). The plan makes coverage decisions on a case-by-case
basis considering the individual Member's health care needs. Pharmacy Medical Necessity Guidelines
are developed for selected therapeutic classes or drugs found to be safe, but proven to be effective in
a limited, defined population of patients or clinical circumstances. They include concise clinical
coverage criteria based on current literature review, consultation with practicing physicians in the
service area who are medical experts in the particular field, FDA and other government agency
policies, and standards adopted by national accreditation organizations. The plan revises and updates
Pharmacy Medical Necessity Guidelines annually, or more frequently if new evidence becomes
available that suggests needed revisions.
This Pharmacy Medical Necessity Guideline does not apply to Uniformed Services Family Health Plan
Members or to certain delegated service arrangements. Unless otherwise noted in the Member’s
benefit document or applicable Pharmacy Medical Necessity Guideline, Pharmacy Medical Necessity
Guidelines do not apply to CareLinkSM Members. For self-insured plans, drug coverage may vary
depending on the terms of the benefit document. If a discrepancy exists between a coverage guideline
and a self-insured Member’s benefit document, the provisions of the benefit document will govern.
4
Pharmacy Medical Necessity Guidelines:
IclusigTM (ponatinib)
Applicable state or federal mandates will take precedence. For Tufts Health Plan Medicare Preferred,
please refer to Tufts Health Plan Medicare Preferred Prior Authorization Criteria.
Treating providers are solely responsible for the medical advice and treatment of Members. The use of
this policy is not a guarantee of payment or a final prediction of how specific claim(s) will be
adjudicated. Claims payment is subject to Member eligibility and benefits on the date of service,
coordination of benefits, referral/authorization and utilization management guidelines when applicable,
and adherence to plan policies and procedures and claims editing logic.
Provider Services
5
Pharmacy Medical Necessity Guidelines:
IclusigTM (ponatinib)