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Changing Patient Care in Multiple Myeloma:
The IMF Nurse Leadership Board’s
Long-Term Survivorship Care Plan
May 13, 2010
San Diego
Accredited by Medical Education Resources
Supported by The International Myeloma Foundation
Grant Funding Provided by Celgene Corporation and
Millennium – The Takeda Oncology Company
1
Welcome and Introductions
Elizabeth Bilotti, RN, MSN, APRN, BC
The John Theurer Cancer Center
at Hackensack University Medical Center
Hackensack, NJ
2
ONS Disclaimer
Meeting space has been assigned to provide a satellite
symposium supported by the International Myeloma
Foundation via an unrestricted educational grant during
the Oncology Nursing Society’s (ONS) 35th Annual
Congress, May 13 - May 16, 2010, in San Diego, CA.
The Oncology Nursing Society’s assignment of meeting
space does not imply product endorsement, nor does
the Oncology Nursing Society assume any responsibility
for the educational content of the symposium.
3
Symposium Accreditation
• This continuing education activity provides 1.5 contact hours.
• Medical Education Resources is an approved provider of
continuing nursing education by the Colorado Nurses
Association, an accredited approver by the American Nurses
Credentialing Center’s Commission on Accreditation.
• Please complete the CE Certificate Registration and Program
Evaluation Form found in your guidebook and return it to the
registration desk at the conclusion of this meeting.
4
Faculty
Chair:
Elizabeth Bilotti, RN, MSN, APRN, BC
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, NJ
Faculty:
Beth Faiman, MSN, APRN-BC,
Tiffany Richards, MS, ANP,
AOCN®
Cleveland Clinic Taussig
Cancer Institute
Cleveland, OH
AOCNP®
MD Anderson Cancer Center
Houston, TX
Teresa Miceli, RN, BSN, OCN®
Joseph D. Tariman, PhC, MN,
Mayo Clinic - Rochester
Rochester, MN
APRN, BC
University of Washington
Seattle, WA
5
Agenda
Time
Discussion Topic
Presenter
12:00 - 12:10 PM
Welcome/Introductions and
Multiple Myeloma Overview
Elizabeth Bilotti
12:10 - 12:30 PM
Update on Current Therapies for the Treatment
of Multiple Myeloma
Beth Faiman
12:30 - 12:45 PM
The NLB’s Long-Term Survivorship Care Plan
Joseph Tariman
12:45 - 1:30 PM
Impact of Myeloma Disease, Treatments, Long-Term Effects,
and Patient-Specific Characteristics on:
12:45 - 1:00 PM
○ Bone Disease and Bone Health
○ Functional Mobility and Safety
Teresa Miceli
1:00 - 1:15 PM
○ Renal Complications
○ Sexuality and Sexual Dysfunctions
Tiffany
Richards
1:15 - 1:30 PM
○ Health Maintenance
Elizabeth Bilotti
1:30 PM
Closing Remarks and Panel Discussion
Elizabeth Bilotti
6
Learning Objectives
• Update on current therapies used in the management
of patients with multiple myeloma (MM)
Provide new data on emergent therapies in MM
•
• Understand how longer survival may lead to a new
•
care paradigm for MM patients
Understand the rationale and value of a Long-Term
Survivorship Care Plan
• Outline the role that nurses play in the implementation
•
of a Survivorship Care Plan
Discuss medical implications of major long-term side
effects associated with novel therapies in MM
7
Multiple Myeloma: Epidemiology
•
Incidence and •
Rates
•
•
Mean Age
Gender
Differences
~1.4% of all cancers
US incidence: 20,580 new cases per year
US prevalence: ~60,000 patients
US deaths: ~10,580 per year
• 62 years for males (75% older than
70 years)
• 61 years for females (79% older than
70 years)
• Affects more men than women (1.3:1)
8
NCCN Multiple Myeloma Guidelines, v.3.2010; Cancer Facts and Figures, 2009; SEER Stat Fact Sheets, Myeloma
(http://seer.cancer.gov/csr/1975_2006/results_merged/sect_18_myeloma.pdf)
Multiple Myeloma: Disease State
• Cancer of plasma cells
• Healthy plasma cells produce antibodies or
immunoglobulins
– Part of our humoral immunity, they are released in
response to foreign body invasion
9
San Miguel JF, et al. Pathogenesis of Multiple Myeloma: Rationale for New and Novel Therapies. Clinical Care Options:
http://clinicaloptions.com/Oncology/Treatment%20Updates/Myeloma/Modules/Pathophysiology/Pages/Page%203.aspx.
Multiple Myeloma:
Abnormal Plasma Cells
Large nuclei (often
eccentric) are present in
multiple myeloma cells.
Multiple Myeloma
(bone marrow aspirate)
10
http://www.healthsystem.virginia.edu/internet/hematology/HessEDD/MalignantHematologicDisorders/MultipleMyelomas/Multiplemyeloma.cfm
Multiple Myeloma Cells Overproduce Monoclonal
Protein and Abnormal Immunoglobulin
• Ineffective immune function
• Decreased normal bone marrow function
• Impaired renal function
Kyle and Rajkumar, N Engl J Med 2004;351:1860-1873
11
Clinical Manifestations
of Multiple Myeloma
Overproliferation of plasma cells can cause:
Infection
Osteolytic
bone
lesions
Hypercalcemia
Bone marrow
suppression
(pancytopenia)
Renal
complications
12
http://myeloma.org/pdfs/ph07-eng_f2.pdf
Major Symptoms at Diagnosis
Symptom
Percent
Presenting
Bone Pain
58%
Fatigue
32%
Weight Loss
24%
Paresthesias
5%
Asymptomatic
11%
13
Kyle RA. Mayo Clin Proc 2003;78:21
Common Sites
for Bone Involvement
• Skull
• Spine
– Thoracic
– Lumbar
– Vertebrae
• Pelvis
• Long bones
14
http://www.emedicine.com/Radio/topic460.htm#section~Introduction
Diagnosing Multiple Myeloma
Three Diagnostic Criteria Required
for a Positive Diagnosis of Multiple Myeloma
1
• Monoclonal plasma cells present in the bone
marrow ≥10%
• Presence of a documented plasmacytoma
2
• Presence of M component in serum and/or urine*
• One or more of the following (CRAB criteria):
3
Calcium elevation (serum calcium >11.5 mg/dL)
Renal insufficiency (serum creatinine >2 mg/dL)
Anemia (hemoglobin <10 g/dL or 2 g/dL <normal)
Bone disease (lytic lesions or osteopenia)
*Monoclonal M spike on electrophoresis IgG >3.5 g/dL, IgA >2 g/dL, light chain >1 g/dL in 24-hour urine sample.
15
Durie et al for the International Myeloma Working Group. Leukemia. 2006:1-7.
Diagnostic Evaluation
of Multiple Myeloma
Test
Finding(s) With Myeloma
CBC with differential counts
↓ Hgb, ↓ WBC, ↓ platelets
Electrolytes
↑ Creat, ↑ Ca+, ↑ Uric acid, ↓ Alb
Serum electrophoresis with quantitative
immunoglobulins
↑ M protein in serum, may have ↓ levels of normal
antibodies
Immunofixation
Identifies light/heavy chain types M protein
β2-microglobulin
↑ Levels (measure of tumor burden)
C-reactive protein
↑ Levels (marker for myeloma growth factor)
24-hour urine protein electrophoresis
↑ Monoclonal protein (Bence Jones)
Bone marrow biopsy
≥10% plasma cells
Skeletal imaging
Osteolytic lesions, osteoporosis
Serum free light chain
↑ Free light chains
MRI
Evaluation of involvement of disease
Alb = albumin; CBC = complete blood count; Creat = creatinine; Hgb = hemoglobin;
MRI = magnetic resonance imaging; WBC = white blood cell
16
Abella. Oncology News International. 2007;16:27; Barlogie et al. In: Williams Hematology. 7th ed. 2006:1501; Durie et al. Hematol J. 2003;4:379;
MMRF. Multiple Myeloma: Disease Overview. 2006. www.multiplemyeloma.org; Rajkumar et al. Blood. 2005;106(3):812.
Durie-Salmon Staging System
for Multiple Myeloma
Stage
Criteria
Myeloma Cell Mass
(x1012 cells/m2)
I
All of the following:
Hemoglobin >10 g/dL
Serum calcium level 12 mg/dL (normal)
Normal bone or solitary plasmacytoma on x-ray
Low M component production rate:
IgG <5 g/dL
IgA <3 g/dL
Bence Jones protein <4 g/24 hr
<0.6 (low)
II
Not fitting stage I or III
0.6 - 1.2 (intermediate)
III
A
B
One or more of the following:
Hemoglobin <8.5 g/dL
Serum calcium level >12 mg/dL
Multiple lytic bone lesions on x-ray
>1.2
High M-component production rate:
IgG >7 g/dL
IgA >5 g/dL
Bence Jones protein >12 g/24 hr
Subclassification criteria:
Normal renal function (serum creatinine level <2.0 mg/dL)
Abnormal renal function (serum creatinine level 2.0 mg/dL)
Durie and Salmon, Cancer 1975;36(9):842-854
(high)
17
Multiple Myeloma Staging: International
Staging System for Symptomatic MM
Stage
Values
Stage 1
ß2M <3.5 mg/dL
ALB 3.5 g/dL
Stage 2
Not Stage 1 or 3
Stage 3
ß2M >5.5 mg/dL
2M=serum 2 microglobulin in mg/dL; ALB=serum albumin in g/dL
• ISS should only be used in patients who meet diagnostic criteria for
myeloma since other conditions (renal dysfunction from diabetes or
hypertension) may cause elevated B2M levels
• ISS is more of a prognostic index; it does not quantify tumor burden or
extent of involvement
• It is recommended that ISS staging be used along with the Durie-Salmon
Staging System
18
Greipp PR, et al. Blood 2005; 102: 190a
Challenges in MM Management
Currently incurable in most patients
Long-term complete responses are rare
Median overall survival for newly diagnosed patients is ~3.7 years
ASCT may prolong progression-free survival, but it’s not curative
Newer drugs improved survival to up to ~2.6 years from relapse
New treatment options are currently
in development with the goal to further improve outcomes
19
NCCN Practice Guidelines v.3.2010; Kumar et al, Blood 111(5), 2008
MM Treatment Options
Treatment Category
Interventions
Conventional
chemotherapy
• Melphalan
• Doxorubicin
• Vincristine
Steroid therapy
• Dexamethasone
• Prednisone
Novel therapies
• Thalidomide
• Lenalidomide
• Bortezomib
Stem cell
transplantation
• Autologous
• Allogeneic
Radiation therapy
• Localized
20
Update on Current Therapies for
the Treatment of Multiple Myeloma
Beth Faiman, MSN, APRN-BC, AOCN®
Cleveland Clinic Taussig Cancer Institute
Cleveland, OH
21
Multi-Drug Combinations
in Multiple Myeloma
Acronym
Multi-Drug Combination
VTD
Bortezomib/Thalidomide/Dexamethasone
VTP
Bortezomib/Thalidomide/Prednisone
VT
VMP
VP
VMPT
Bortezomib/Thalidomide
Bortezomib/Melphalan/Prednisone
Bortezomib/Prednisone
Bortezomib/Melphalan/Prednisone/Thalidomide
VDR
Bortezomib/Dexamethasone/Lenalidomide
VDC
Bortezomib/Dexamethasone/Cyclophosphamide
VDCR
Bortezomib/Dexamethasone/Cyclophosphamide/Lenalidomide
Rd/RD
Lenalidomide/Dexamethasone
VAD
Vincristine/Doxorubicin/Dexamethasone
MP
Melphalan/Prednisone
MPT
Melphalan/Prednisone/Thalidomide
MPR
Melphalan/Prednisone/Lenalidomide
DVD
Doxorubicin/Vincristine/Dexamethasone
22
NCCN Review Categories
NCCN
Category
Transplant
Non-Transplant
NCCN
Category
Bortezomib/Dexamethasone*
1
Bortezomib/Melphalan/Prednisone (VMP)
1
Bortezomib/Thalidomide/
Dexamethasone (VTD)*
1
Melphalan/Prednisone/Thalidomide (MPT)
1
Lenalidomide/Dexamethasone*
1
Lenalidomide/Low Dexamethasone*
1
Bortezomib/Doxorubicin/
Dexamethasone*
1
Melphalan/Prednisone (MP)
2A
Dexamethasone*
2B
Vincristine/Doxorubicin/Dexamethasone (VAD)*
2B
L-Doxorubicin/Vincristine/
Dexamethasone (DVD)*
2B
Thalidomide/Dexamethasone*
2B
Thalidomide/Dexamethasone*
2B
Dexamethasone*
2B
Bortezomib/Lenalidomide/
Dexamethasone (VRD)
2B
L-Doxorubicin/Vincristine/Dexamethasone
(DVD)
2B
*Combinations recently reviewed by NCCN
Generic Name
Bortezomib
Lenalidomide
Thalidomide
NCCN Clinical Practice Guidelines in Oncology, v.3.2010
Trade Name
Velcade
Revlimid
Thalomid
Company
Millennium - Takeda
Celgene
Celgene
23
NCCN: Changing
Categories of Consensus
• Change is a natural process secondary to the
constant stream of data from recent
clinical studies
• Categories 2A and 2B are not indicative of
inferiority of the treatment:
…non-uniform consensus does not represent a major
disagreement, rather it recognizes that given imperfect information,
institutions may adopt different approaches. A Category 2B
designation should signal to the user that more than one approach
can be inferred from the existing data…
NCCN, “Categories of Evidence and Consensus”, 2010
24
NCCN, “Categories of Evidence and Consensus”, 2010
Revised Categories of Evidence and
Consensus – NCCN Guidelines, 2010
Previous
Category
New
Category
Bortezomib/Dexamethasone
2B
1
Bortezomib/Thalidomide/Dexamethasone (VTD)
2B
1
Lenalidomide/Dexamethasone
Lenalidomide/Low Dexamethasone
2B
2B
2B
1
1
1
Thalidomide/Dexamethasone
2A
2B
Dexamethasone
2A
2B
Vincristine/Doxorubicin/Dexamethasone (VAD)
2A
2B
L-Doxorubicin/Vincristine/Dexamethasone (DVD)
2A
2B
Multiple Myeloma Therapy
Bortezomib/Doxorubicin/Dexamethasone
NCCN Categories of Evidence and Consensus:
1
High-level evidence, uniform consensus
2A Lower-level evidence, uniform consensus
2B Lower-level evidence, non-uniform consensus
25
NCCN Clinical Practice Guidelines in Oncology, v.3.2010
Future of MM Therapy: Recent
and Ongoing Clinical Studies
Patient Treatment Largely Determined by Transplant Status
• Transplant-ineligible patients
– VMP – VT vs. VTP – VP
– VMPT – VT vs. VMP
• Lenalidomide/dexamethasone in
smoldering myeloma
– QUIREDEX Study
– MP vs. MPT
– MP vs. MPR vs. MPR
(continued lenalidomide)
• Transplant-eligible patients
• New combinations and early studies
– EVOLUTION Study
– Lenalidomide after ASCT
– Pomalidomide/low dexamethasone
– MPR vs. high-dose melphalan
– Carfilzomib
– Carfilzomib/lenalidomide/dexamethasone
– Elotuzumab/lenalidomide/dexamethasone
26
ASCO 2009; ASH 2009
VMP vs. VTP Followed by VT vs. VP
(ASH 2009 - PLENARY SESSION)
A Phase 3 Study of Bortezomib/Melphalan/Prednisone (VMP) vs.
Bortezomib/Thalidomide/Prednisone (VTP) Followed by
Bortezomib/Thalidomide (VT) vs. Bortezomib/Prednisone (VP) in
Elderly Newly Diagnosed Multiple Myeloma (NDMM) Patients
• Study objective:
– Testing an alkylating agent (melphalan) and an immunomodulatory
drug (thalidomide) as a partner for bortezomib
• Study design:
– Prospective, multicenter, randomized
– Induction: patients randomized to 6 cycles of VMP vs. VTP
– Maintenance: patients randomized to VT vs. VP for up to 3 years
27
Mateos et al, Blood 114, Abstract 3, 2009
Conclusions from VMP – VT vs.
VTP – VP
≥PR, %
CR, %
CR/nCR, %
TTP, %
PFS, %
OS, %
VMP
81
22
36
75
71
81
VTP
79
27
36
70
61
84
Induction
Maintenance
CR, %
1Y TTP, %
1Y OS, %
VT
46
84
92
VP
38
71
89
p-Value
NS
0.05
NS
• Both induction schedules are highly effective with similar overall response
rate (ORR) and complete response (CR)
– More neutropenia but less cardiac toxicity and peripheral neuropathy with VMP
• Both maintenance therapies markedly improve responses
• Combination of these regimens improves poor prognosis of high-risk
cytogenic abnormalities (CA) in elderly MM patients
28
Mateos et al, Blood 114, Abstract 3, 2009
Bortezomib/Melphalan/Prednisone/Thalidomide –
Bortezomib/Thalidomide
A Phase 3 Study of VMPT Followed by Maintenance With Bortezomib and
Thalidomide for Initial Treatment of Elderly Multiple Myeloma Patients
• Study Objective:
– Compare VMPT with a maintenance regimen including bortezomib and
thalidomide to VMP without a maintenance regimen
• Study Design:
– Prospective, randomized
Bortezomib 1.3 mg/m2
Melphalan 9 mg/m2 Days 1-4
Prednisone 60 mg/m2 Days 1-4
Thalidomide 50 mg
Days 1-42
Bortezomib 1.3 mg/m2
Melphalan 9 mg/m2 Days 1-4
Prednisone 60 mg/m2 Days 1-4
Bortezomib 1.3 mg/m2 Days 1,15
Thalidomide 50 mg/day continuously
No Maintenance
– Both regimens amended to nine 5-week cycles
– Bortezomib modified to weekly administration (days 1,8,15,22)
29
Palumbo et al, Blood 114, Abstract 128, 2009
Conclusions from VMPT – VT vs. VMP
Study Arm
PR, %
VGPR, %
CR, %
2Y PFS, %
2Y OS, %
VMPT-VT
86
55
34
70
89.6
VMP
79
47
21
58.2
89.0
0.02
0.07
0.0008
0.0008
0.84
p-Value
• VMPT followed by VT was superior to VMP for response rates and PFS.
• The weekly infusion of bortezomib significantly reduced the incidence of
grade 3-4 peripheral neuropathy
– From 18% to 4% (p=0.0002) in VMPT arm
– From 13% to 2% (p=0.0003) in VMP arm
• This is the first report showing the superiority of a 4-drug regimen
followed by maintenance compared to standard therapy (VMP)
30
Palumbo et al, Blood 114, Abstract 128, 2009
Melphalan/Prednisone vs.
Melphalan/Prednisone/Thalidomide
MP vs. MPT as Initial Therapy for Previously Untreated Elderly and/or
Transplant-Ineligible Patients With Multiple Myeloma: A Meta-Analysis of
Randomized Controlled Trials
• Study objective:
– Systemic review of randomized controlled trials to compare
efficacy of MP with MP+T
– Clinical endpoints are response rate (RR), progression-free
survival (PFS), and overall survival (OS)
• Study design:
– Comprehensive search of database to identify randomized
controlled trials
– Meta-analysis by pooling results on clinical endpoints
31
Kapoor et al, Blood 114, Abstract 615, 2009
Conclusions from MP vs. MPT
• Five prospective randomized controlled trials
were identified (1571 patients data analyzed)
• The data indicated that MPT was better than
MP in achieving at least a partial response.
• The pooled hazards ratios for PFS and OS
were in favor of MPT
• Analyses suggest that MPT is superior to MP
in terms of response and survival
32
Kapoor et al, Blood 114, Abstract 615, 2009
MP vs. MPR vs. MPR – R
A Phase 3 Study to Determine the Efficacy and Safety of Lenalidomide in
Combination With Melphalan and Prednisone (MPR) in Elderly Patients
With NDMM
• Study objective:
– In previous studies lenalidomide was effective in relapsed/refractory MM
– Compare safety and efficacy of MPR in NDMM patients
• Study design:
Melphalan
0.18 mg/kg
Prednisone
2 mg/kg
Lenalidomide 10 mg QD PO
Days 1-4
Days 1-4
Days 1-21
Lenalidomide
Melphalan
0.18 mg/kg
Prednisone
2 mg/kg
Lenalidomide 10 mg QD PO
Days 1-4
Days 1-4
Days 1-21
Placebo
Melphalan
Prednisone
Placebo
Days 1-4
Days 1-4
Days 1-21
Placebo
0.18 mg/kg
2 mg/kg
Palumbo et al, Blood 114, Abstract 613, 2009
Progression
Cycles 10+
Nine 28-day cycles
Lenalidomide
33
Conclusions From MP vs. MPR
vs. MPR – R
ORR, %
CR, %
≥ VGPR, %
PR, %
MPR-R (152)
77
18
32
45
MPR (153)
67
13
33
34
MP (154)
49
5
11
37
Study Arm (Patients)
• MPR – R regimen reduced risk of progression by
50% vs. MP alone
• MPR followed by lenalidomide maintenance is a
new therapeutic option
• This regimen can be considered a new standard
for elderly patients
34
Palumbo et al, Blood 114, Abstract 613, 2009
Lenalidomide After ASCT
First Analysis of a Phase 3 Study of the Intergroupe Francophone
Du Myelome (IFM 2005 02)
• Study objective:
– Controlling the residual disease after high-dose therapy
• Neuropathy a major limiting factor in previous study
– Lenalidomide evaluated (has lower neurological toxicity)
• Study design:
– Prospective, randomized, placebo-controlled
– 1st line ASCT less than 6 months before enrollment
– Consolidation with lenalidomide, 25 mg/day, po, 21 days/month,
2 months
– Maintenance until relapse
• Lenalidomide, 10-15 mg/day
35
Attal et al, Blood 114, Abstract 529, 2009
Conclusions From
Lenalidomide After ASCT
Post-Consolidation
Category Improvement
Patients
Patient Status
CR to
sCR
VGPR to
CR/sCR
PR to
VGPR/CR/sCR
5
29
25
sCR/CR Rate
Pre-consolidation
0.1
Post-consolidation
0.144
p-Value
0.0005
2-month consolidation with lenalidomide:
– 80% of patients were able to receive the planned
2 cycles of consolidation
– Significantly improved the sCR/CR rate
36
Attal et al, Blood 114, Abstract 529, 2009
Melphalan/Prednisone/Lenalidomide
vs. High-Dose Melphalan
MPR vs. Melphalan (200 mg/m2) and Autologous Transplantation in Newly
Diagnosed Myeloma Patients: An Interim Analysis
• Study objective:
– To compare melphalan/prednisone/lenalidomide (MPR) with tandem
melphalan (200 mg/m2) in patients younger than 65 years
• Study design:
– Induction: four 28-day cycles
• Lenalidomide 25 mg days 1-21
• Low-dose dexamethasone 40 mg days 1,8,15,22
– Consolidation:
• MPR arm: six 28-days cycles
– Melphalan 0.18 mg/kg days 1-4
– Prednisone 2 mg/kg days 1-4
– Lenalidomide 10 mg days 1-21
• Melphalan arm: tandem melphalan 200 mg/m2 with stem cell support
37
Palumbo et al, Blood 114, Abstract 350, 2009
Conclusions From MPR vs. MEL200
Rd Induction
PR
VGPR
CR
Response, at least, %
84
27
5
1 Year
PFS, %
1 Year
OS, %
Neutropenia, %
Thrombocytopenia,
%
Infections
%
GI
%
MPR
96
98
34
16
3
1
MEL200
94
99
97
97
21
17
p-Value
n/a
n/a
<0.001
<0.001
<0.001
<0.001
Consolidation
Arm
• Rd is an effective and safe induction regimen
• Both MPR and MEL200 improved the quality of response.
– At one-year follow-up, PFS and OS are similar in both groups.
– Longer follow-up is needed
38
Palumbo et al, Blood 114, Abstract 350, 2009
Lenalidomide/Dexamethasone
in Smoldering Myeloma
Phase 3 Trial of Lenalidomide/Dexamethasone vs. Therapeutic
Abstention in Smoldering Multiple Myeloma (sMM) at High Risk
of Progression to Symptomatic MM
• Study objective:
– To investigate whether early treatment prolongs the time to
progression (TTP) in sMM patients at high risk
• Study design:
– Multicenter, randomized, open-label
– High-risk population defined by plasma cells ≥10%
and M-component ≥3 g/dL
– Len/dex arm, nine 4-week cycles:
• Lenalidomide: 25 mg/daily, days 1-21
• Dexamethasone: 20 mg/daily, days 1-4 and 12-15 (total dose 160 mg)
• Maintenance with lenalidomide, 10 mg on days 1-21 every 2 months
until progression
Mateos et al, Blood 114, Abstract 614, 2009
39
Conclusions From Lenalidomide/Dexamethasone
in Smoldering Myeloma
Interim Analyses
Patients
PR
%
VGPR% CR%
Evaluable patients
40
53
21
Completed 9 cycles
16
53
27
sCR
%
ORR
%
11
5
90
13
7
100
• In sMM patients, lack of treatment is associated with
early progression (17.5 months) with bone disease
• Lenalidomide/dexamethasone treatment prolonged TTP
and induced CRs with a manageable and acceptable
toxicity profile
40
Mateos et al, Blood 114, Abstract 614, 2009
Emerging New Treatments
in Early Development
• EVOLUTION phase 2 study
– Novel 3- and 4-drug combinations: VDR, VDC, VDCR
– Exploring the combination of bortezomib and dexamethasone with
lenalidomide and cyclophosphamide in NDMM patients
• Development of a novel proteosome inhibitor, carfilzomib
– Appears to work in patients that are resistant to bortezomib
– Prior therapy with bortezomib doesn’t preclude a good response
– Minimal neuropathy and myelosuppression
• Development of pomalidomide, an immunomodulatory drug
– Evidence of efficacy in heavily pretreated patients with
relapsed disease
– Acceptable safety profile
• Development of elotuzumab, a monoclonal antibody against a
glycoprotein that is highly and uniformly expressed in MM
– Manageable toxicity profile in combinations with other agents
– Promising preliminary efficacy data
41
ASCO 2009; Kumar et al, Blood 114, Abstract 127, 2009; Lonial et al, Blood 114, Abstract 432, 2009; Richardson et al, Blood 114, Abstract 301,
2009; Siegel et al, Blood 114, Abstract 303, 2009; Wang et al, Blood 114, Abstract 302, 2009; Niesvizky et al, Blood 114, Abstract 304, 2009
Future Direction of Combinations
& Protocols With Novel Therapies
• Evolving role of the new drug combinations for
transplant-eligible and -ineligible patients
– New 4-drug aggressive regimen (VMPT)
– New strategy for bortezomib: weekly dose with much better
tolerability
• Two new clinical paradigms are emerging:
– Control option
• Careful use of drugs, using agents sequentially
– Cure option
• Aggressive treatment
Treatment of smoldering MM patients provided first evidence of
efficacy in preventing progression.
42
ASCO 2009; ASH 2009
Conclusions
• Novel combination therapies exhibit great
potential in improving RR, TTP, PFS, and
OS outcomes
• Randomized clinical trials are underway to
compare which of these novel combinations
will offer patients better OS balanced with a
good quality of life
43
The NLB’s Long-Term
Survivorship Care Plan
Joseph Tariman, PhC, MN, APRN, BC
University of Washington
Seattle, WA
44
Why Survivorship Care
for Multiple Myeloma?
Increased survival leads to the need for new
approaches to quality survivorship care
Long-term care management offers the
opportunity to enhance the patient’s treatment
outcome and quality of life
45
Multiple Myeloma Patients Are
Living Longer Post Diagnosis
Age
Group
Relative Survival, %
1990-1992
2002-2004
Increase, %
P Value
5-year relative survival
<50
44.8
56.7
11.9
0.001
50 – 59
38.8
48.2
9.4
0.001
60 – 69
30.6
36.3
5.7
0.09
70 – 79
27.1
28.7
1.6
0.21
All ages
28.8
34.7
5.9
<0.001
10-year relative survival
<50
24.5
41.3
16.8
<0.001
50 – 59
17.2
28.6
11.4
<0.001
60 – 69
10.8
15.4
4.6
0.03
70 – 79
7.4
10.4
3.0
0.09
All ages
11.1
17.4
6.3
<0.001
46
Brenner et al, Blood, 2008
Individuals Diagnosed With MM
Are Living Longer
The Kaplan-Meier curves for overall survival from diagnosis:
A.Groups are divided based on the time of diagnosis:
• After 12-31-1996
• On or before 12-31-1996
B.Grouped into 6-year intervals based on the date of diagnosis
47
Kumar et al, Blood, 2008
Reprinted by permission from the American Society of Hematology
Post-Transplantation Relapsed
Patients Are Also Living Longer
The Kaplan-Meier curves for overall survival from the time of
post-transplantation relapse:
A. Grouped into 2-year intervals based on the date of relapse
B. Grouped by whether the patients were treated with one or more newer drugs
– Thalidomide
– Lenalidomide
– Bortezomib
48
Kumar et al, Blood, 2008
Reprinted with permission from the American Society of Hematology
Assessment of Early
Overall Survival
• 1-year survival steadily improving
–
–
–
–
–
–
–
R/low-dexamethasone
Total therapy 2
VMP (VISTA)
R/dexamethasone
ASCT
MPT
Thalidomide/dexamethasone
96%
92%
90%
88%
88%
87%
80–83%
Increased survival leads to the need for new
approaches to quality survivorship care
49
Barlogie et al. N Engl J Med 2006; Facon et al. Lancet 2007; Palumbo et al, Lancet 2006; Rajkumar et al J Clin Oncol 2006; Rajkumar et al J Clin Oncol
2008; Rajkumar et al ASH 2008; San Miguel et al N Engl J Med 2008;
Nurse-Centric Model
of Survivorship Care*
Nurses are central to
patient management and
healthcare resource
coordination.
Patient Monitoring
Patient Management
Patient Counseling
Patient Research
Nursing roles emerge as
central to survivorship
care.
Patient Advocacy
Patient Education
50
* Developed by ScienceFirst, LLC; All Rights Reserved (www.science-first.com)
International Myeloma Foundation’s
Nurse Leadership Board
A partnership with multiple myeloma nurses to gain insights into
their unmet needs and to address them and those of their patients
by accomplishing the following objectives:
• Provide insights into the needs of myeloma
nurses and their patients
• Identify and implement key nurse and patient
education programs
• Facilitate information flow between the IMF,
oncology nursing organizations, and
patients
51
Meeting the Unmet Need
Opportunity to leverage the NLB’s experience by
identifying relevant side effects and developing a
Long-Term Survivorship Care Plan for
Multiple
Myeloma
• Survivorship Care Plan will enhance the
patient’s treatment outcome and quality of life.
• Survivorship Care Plan will need to be updated
as new therapies emerge
52
First Step: Consensus Guidelines
for Management of Acute Side Effects
NLB determined the 5 most common emergent
side effects requiring clinical “Consensus
Statement” development.
Managing the Side Effects of Novel Agents
for Multiple Myeloma: Guidelines and
Patient Education Sheets – NLB 2008
Clinical Journal of Oncology Nursing –
Supplement to Vol. 12 (3)
Peripheral neuropathy
DVT and PE
Myelosuppression
GI effects
Steroid effects
53
IMF-NLB ‘Consensus Statements’ supplemCJON June 2008
NLB Dissemination
• 2010 NLB Speaker Programs: “Consensus on Care”
– 10 programs in 10 cities
•
•
•
•
•
•
•
•
Speakers at IMF Patient & Family Seminars
Speakers at IMF Regional Community Workshops
NLB poster at the XII International Myeloma Workshop
NLB blogged at the XII International Myeloma Workshop
Articles appear in Myeloma Today
Hold informational conference calls with support groups
Participate as faculty at the annual ONS meeting
Participate in advocacy initiative – Hill visits and in the
communities
• Run patient advisory boards
54
Next Step: Developing a Long-Term
Survivorship Care Plan
Evidence-based data for 5 major long-term side-effect
issues and their management: creation of clinical
practice-based consensus documents
Bone Health &
Bone Disease
Functional
Mobility
Sexuality &
Sexual
Dysfunction
Renal
Complications
Health
Maintenance
Outcome: Survivorship Care Plan and Manuscript
55
Defining Cancer Survivorship
The process of living with,
through, and beyond cancer.
By this definition, cancer
survivorship begins at
diagnosis. It includes people
who continue to have
treatment either to reduce risk
of recurrence or to manage
chronic disease
(ASCO, 2009)
56
Comparisons of Patient and Physician
Expectations for Cancer Survivorship Care
Investigators from the Harvard School of Public Health,
Dana-Farber Cancer Institute, and the Institute
of Clinical Evaluative Sciences (Toronto) conducted a
study to compare expectations regarding survivorship
care among PCPs, oncologists, and patients.
• The results demonstrated a lack of agreement among
these constituents with respect to their roles in ongoing
survivor care
• The discordance was particularly high between patients
and their oncologists. The underlying causes for the
discrepancies were unclear
57
Cheung et al, JCO 2009
Barriers to Cancer Survivor Care
+
58
Challenges to Survivorship Care
As lives are extended, so too are the risks of
developing late or delayed effects
• Major question: Who will be
responsible for
–
–
–
–
Monitoring patient’s health?
Assisting in recovery?
Making referrals?
Paying for continued care?
59
Leigh, Cancer Survivorship: A Nursing Perspective, in Cancer Survivorship Today and Tomorrow, 2007
Cancer Survivorship:
From Individual to Experience
• Defined as
– A time frame
– A stage or phase
– An outcome
• Must take into account
–
–
–
–
–
–
Maintenance therapy
Incurable but treatable cancers
Regimen changes
Recurrences
Secondary malignancies
Late effects of treatments
• General health maintenance
60
Cancer Survivorship Care:
“Why Is it Important?”
Institute of Medicine (IOM) Findings
• Cancer survivorship has tripled to 10
million over the past 30 yrs in the US
• Impacting cost on healthcare system
• High elderly population (~6 million)
• One in nine adult cancer survivors
under age 65 is uninsured
• Lack of guidelines for survivors
• Most will return to work, but one in 5
will have cancer-related limitations up
to 5 yrs later
61
Shulman & Ganz ASCO Survivorship Models 2008
IOM Findings:
Survivorship Care (cont’d)
IOM Recommendation:
• “All patients completing Rx
should receive a
comprehensive treatment
summary & care plan.”
62
Shulman & Ganz ASCO Survivorship Models 2008
IOM Recommendations
for Quality Healthcare in America
•
•
•
•
•
•
•
•
•
•
Care based on continuous healing relationships
Customized care
Patient as source of control
Shared knowledge and information
Evidence-based decision making
Safety as a system property
Transparency
Anticipation of needs
Continuous decrease in waste
Cooperation
63
Reasons for a Survivorship
Care Plan
• Summarize treatment
• Communicate late effects of
disease and treatment
• Promote interactions between
patients and healthcare providers
• Promote a healthy lifestyle
– Prevent early recurrence
– Reduce risk of co-morbid conditions
64
Shulman & Ganz ASCO Survivorship Models 2008
What Is a Survivorship Care Plan?
• A document
– Summarizes what transpired during
cancer treatment
– Gives recommendations for follow-up care
• It needs to
– Be prospective
– Identify known and potential long-term effects
• It aims to
–
–
–
–
Promote a healthy lifestyle
Prevent recurrence of cancer
Reduce risk of co-morbid conditions
Ensure adherence to follow-up
recommendations
Implementing Cancer Survivorship Care Planning http://www.nap.edu/catalog/11739.html
65
Key Elements for Cancer
Survivorship Care Planning
66
Shulman & Ganz ASCO Survivorship Models 2008
Creation of a Long-Term Survivorship
Care Plan in Multiple Myeloma
• Co-morbid conditions affect
– Treatment options
– Survival
– Late side effects
• The plan will
– Prevent and control
• Adverse cancer diagnosis
• Treatment-related outcomes
– Late effects of treatment
– Second cancers
– Suboptimal quality of life
– Provide a knowledge base for follow-up care
and surveillance
– Optimize health during cancer treatment
67
Long-Term Care Plan:
Recommendations for Clinicians
Excerpt of the Recommendations for Clinicians: Renal Health
68
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Long-Term Care Plan:
Patient Tear-Out Tool
Excerpt of the Patient Tear-Out Tool: Renal Health
69
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Essentials of Survivorship Care
• Prevention and detection of
new cancers and recurrence
• Intervention for consequences of
cancer and its treatment
(eg, diabetes)
• Coordination between
specialists and primary care
providers
70
Goals of NLB
Survivorship Care Plan
Develop recommendations for schedules of
evaluations and evidenced-based
interventions:
• Enable clinicians and patients to optimize therapy
by preventing or adequately treating co-morbid
conditions.
71
Goals of NLB
Survivorship Care Plan (cont’d)
NLB will disseminate this information to
those within the community who can
affect the most change:
• Patients
• Caregivers
• Healthcare providers
72
Survivorship Care Continuum
Individuals with chronic or intermittent disease may
receive ongoing treatment for their disease, but benefit
from survivorship care as they live with their disease
Prevention
Initial
treatment
Diagnosis
Continuing
care
Follow-up
Recurrence
Progressive
disease
Maintenance
Palliative care
Survivorship isn’t a stage!!!!
It is a continuum from diagnosis through the patient’s life.
73
Impact of Myeloma Disease,
Treatments, Long-Term Effects, and
Patient-Specific Characteristics on:
Bone Disease and Bone Health
Functional Mobility and Safety
Teresa Miceli, RN, BSN, OCN®
Mayo Clinic – Rochester
Rochester, MN
74
Bone Disease in Multiple Myeloma
Bone destruction is a hallmark of multiple myeloma.
Caused by defects in the
balance between bone
formation and resorption
• Osteoblast inhibition and
activation of osteoclasts
Osteolysis often present
in multiple myeloma
bone marrow biopsy
• 80% to 90% of patients will have
osteoporotic and osteolytic bone
lesions at some time during the
course of their disease
75
http://www.wheelessonline.com/ortho/multiple_myeloma; http://www.uams.edu/radiology/info/clinical/pet/images.asp
Bone Disease in Multiple Myeloma (cont’d)
• Bone disease is the major cause of morbidity
and mortality, leading to
– Pathological fractures
– Spinal cord compression and neurological changes
– Severe pain (~60%)
– Hypercalcemia (30%)
• Prognostic implications
– Increased number of lesions correlates with poorer
prognosis
– Co-morbid sequelae
Skeletal events may progress despite continued treatment
76
http://www.wheelessonline.com/ortho/multiple_myeloma
Consequences of Bone Disease
Functional mobility
– Pain
– Limits normal activities of daily living
– Impact on employability
– Neurological changes due to vertebral
compression fractures
• Paralysis
• Chronic paresthesia
Psychological impact
– Depression, sexual dysfunction,
body image
– Quality of life
77
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Bone Health and Bone Disease:
Summary of Treatments
Management of multiple myeloma-related bone disease
involves treatment of the underlying disease!
Therapy
Bortezomib
Comments
Affects osteoclast functions, reduces resorption. May
increase osteoblast activity and induce bone formation.
Thalidomide
Immunomodulators
Lenalidomide
Decrease osteoclast formation, may positively affect
bone formation and prevent resorption.
Pomalidomide
Dexamethasone
Steroids
Induces apoptosis.
Prednisone
Radiation Therapy
Component of general therapy and palliation. Alleviation
of pain and neurological problems.
Surgery
Prevention of impending fracture. Vertebroplasty and
balloon kyphoplasty for vertebral compression fractures.
Bisphosphonates
Standard of care for myeloma-related hypercalcemia,
bone pain, and skeletal lesions.
78
Roodman, Am S Hem Ed Prog 2008; Yeh & Berenson, Clin Cancer Res 2006; Fitch & Maxwell, Oncol Nurs Forum 2008; Berenson et al, JCO
2002; Pennisi et al, Am J Hematol 2009; Cady et al, J Am Coll Surg 2005; Faiman et al, Clin J Onc Nurs 2008
Bone Health and Bone Disease:
Position Statement
• Improvement in OS makes effective skeletal care critically
important in MM patients
• Oncology healthcare providers play a key role.
– Monitoring for bone disease and related sequelae
– Maintaining adequate bone health
• Nurses need to provide interventions that promote bone
health maintenance to improve mobility and enhance
quality of life
• NLB to enact a plan of care that encompasses the needs
of MM survivors along their care spectrum
79
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Strategic Recommendations
Osteoporosis and osteolytic bone lesions have clinical
implications and impact quality of life.
•
•
•
•
Assess and treat bone disease and bone-related sequelae
Monitor regularly for bone pain and bone-related complications
Assess impact of MM therapeutics on bone health
Include risk factors present due to co-morbid conditions to optimize
treatment plan
• Institute interventions and management strategies based on the
patients disease state
– Active disease
– Remission
80
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Evidence-Based Recommendations
• Mobility and exercise
• Dietary recommendations and supplements
• Regular assessment of bone disease and bone health
(lab and imaging)
• Radiation treatment
• Surgical interventions and post-surgery care
• Use of bisphosphonates
• Effective pain management
• Healthcare Provider Tool
• Patient Education Tool
81
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Functional Mobility and Safety
in Multiple Myeloma
• Multiple myeloma occurs more commonly
in the elderly population
• Bone disease is a major component of
multiple myeloma
• Inherent to this and other risk factors are
issues of mobility and safety.
– Up to 1/3 of older adults fall every year
– In myeloma, falls often lead to fractures
82
Roodman, Leukemia 2008; Roodman, Hem Am Soc Hematol Educ Program 2008; Melton et al, J Bone Miner Res 2004
Risk Factors Affecting Functional
Mobility in Multiple Myeloma Patients
Factors Contributing to High Risk of Falls (ROF):
Sensory Issues
• Vision
• Hearing
Age-Related
Co-Morbidities
• Cardiovascular
• Diabetes
• Osteoporosis
• Hormonal status
• Parkinson’s disease
• Dementia
• Urinary incontinence
• Arthritis
Nutrition
• Muscle weakness
• Weight loss
Psychological Issues and Lifestyle
83
Gantz et al, J Am Med Assoc 2007
Side Effects’ Impact on Functional
Mobility and Safety
Common SE
Peripheral neuropathy
– Sensory and motor symptoms
– Ataxia
Muscle wasting
– Tone and mass
– Strength and motor function
Myelosuppression
– Thrombocytopenia
– Neutropenia
– Anemia
Gastrointestinal symptoms
– Nausea, vomiting, constipation, diarrhea
– Dehydration, anorexia, weight loss
– Hypercalcemia, hypokalemia, hyponatremia
Effects on Functional Mobility
• Discomfort or prescribed limitations by the
health practitioner
• Pain and/or discomfort
• Lack of desire to participate in activity and
• Inability to mobilize safely
• Lack of ability to withstand extended activity
• May require oxygen
Inability to participate in activities due to
organ-function restrictions as prescribed by
healthcare provider
Fatigue and somnolence
• Mobility limitations due to these symptoms
• Cognitive changes related to pain medication
Cardiovascular issues
• Difficulty in desire or ability to participate in
activities of daily living, including exercise,
diet, etc, and impact on overall quality of life
– Deep vein thrombosis
84
CJON June 2008, 12(3) suppl.
Functional Mobility and Safety:
Position Statement
• Mobility issues and ROF pose serious challenges to
MM patients
• Oncology healthcare providers need to help patients to
achieve improvements in functional ability, strength, and
balance to reduce ROF and fall-related injuries
• NLB to enact a plan of care that includes assessment,
evaluation, intervention, and education for reducing
symptoms and enhancing functional capacity
• NLB recommendations to advocate health maintenance as
an integral part in preserving mobility
85
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Strategic Recommendations
Functional mobility and ROF have clinical implications,
and impact quality of life and safety.
• Assess level of activity and factors affecting mobility
• Routinely assess for factors that increase ROF
• Institute interventions and management strategies:
– Safe mobility and physical activity programs tailored to the needs
of each patient
– Incorporate nutrition
86
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Evidence-Based
Recommendations
• Overall assessment (medications, lab, and
diagnostic tests)
• Risk factor and falls risk assessment
• Planned physical activity
– Type of physical activity guidelines
– Regular exercise regimen/program
• Dietary recommendations and nutrition
• Healthcare Provider Tool
• Patient Education Tool
87
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Impact of Myeloma Disease,
Treatments, Long-Term Effects, and
Patient-Specific Characteristics on:
Renal Complications
Sexuality and Sexual Dysfunction
Tiffany Richards, MS, ANP, AOCNP®
MD Anderson Cancer Center
Houston, TX
88
Renal Complications and
Disease in Multiple Myeloma
• Kidney dysfunction is one of the
common clinical features of
symptomatic MM.
• Between 20% and 60% of MM
patients present with renal
insufficiency or renal failure at
diagnosis or throughout their disease.
– It may negatively affect overall
survival and quality of life.
89
Tariman and Faiman, in Cancer Nursing Principles and Practice, 2010; Blade et al, Arch Intern Med, 1998
Manifestations and
Pathogenesis of Kidney Failure
• Manifestations of renal disease
–
–
–
–
Elevated serum creatinine level
Anemia and fatigue
Fluid and electrolyte imbalances
Renal failure requiring:
• Dialysis
• Medication modification
• Dietary precautions
• Pathogenesis and factors impacting
renal functions
–
–
–
–
–
Hypercalcemia
Dehydration
Medications
Light chain infiltration
Co-morbid conditions (diabetes, etc)
90
Lokhorst, in Mehta & Singhal, eds. Myeloma 2002; Dimopoulos et al, Leukemia 2008; Tariman et al, Cancer Nurs Princ Pract 2010 (in
press); Rajkumar & Kyle, Mayo Clin Proc 2005; NKF, Am J Kidney Dis 2002
Risk Factors Impacting Renal Functions
in Multiple Myeloma Patients
• Co-morbidities
– Diabetes
– Cardiovascular disease
– Hypertension
• Hereditary and social factors
– Age >60 years
– Racial or ethnic status
– Family history of renal disease
Infections
Anemia
• Treatment side effects
• Kidney disease exacerbates progression of
multiple myeloma
– Failure to maintain proper levels of calcium and phosphorus
in blood
– Limited treatment options due to kidney complications
91
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Renal Complications and Disease:
Summary of Novel Multiple Myeloma
Treatment Effects
Immunomodulators
Thalidomide
Side Effects and
Clinical
Observations
Recommendations
Lenalidomide
Bortezomib
Considered safe in renal
insufficiency
• Caution must be exercised,
as it is mainly excreted
through the urine.
• Renal insufficiency has
been linked to increased
myelosuppression in
patients with decreased
creatinine clearance.
• Safe and effective in
renal failure and
dialysis-dependent
patients.
• May result in renal
recovery in patients
requiring dialysis in
relapsed myeloma.
Dosage adjustments are
not recommended.
• Dose adjustments based on
creatinine clearance
• Regular monitoring CBC
especially in those patients
with creatinine clearance
<60 mL/minute
Dosage adjustments are
not recommended.
92
Celgene Corporation, Revlimid (lenalidomide) [package insert], 2006; Chanan-Khan et al, Blood 2007
Renal Complications:
Position Statement
• Renal insufficiency and failure is one of the common
clinical features of symptomatic multiple myeloma at
presentation or throughout the disease
• Oncology nurses can identify patients at risk for kidney
damage and need to institute therapeutic and
preventive interventions
• NLB to enact a plan of care that addresses therapeutic
and diagnostic interventions for the management of MM
in the context of poor renal function
93
Longo & Anderson, K. Plasma cell disorders. In Harrison's principle of internal medicine 2005
Strategic Recommendations
Renal dysfunction and renal insufficiency are common clinical
features in MM patients and have to be aggressively managed.
•
•
•
•
Early identification of renal impairment
Diagnosis and interventions throughout therapy
Educational and preventive strategies
Myeloma-specific drug therapies
– Alleviation or exacerbation of side effects
• Recommendations for long-term care
• Surveillance for chronic kidney disease
94
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Evidence-Based Recommendations
•
•
•
•
•
Diagnosis of renal insufficiency
Impact of MM therapies on renal function
Additional risk factors and co-morbidities
Attendant bone complications
Newly diagnosed patients – transplant eligible and
transplant ineligible
• Patients on dialysis
• Monitoring
• Healthcare Provider Tool
• Patient Education Tool
95
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Sexuality & Sexual Dysfunction
Sexual dysfunction (SD) is characterized by those psychological
and physiological changes that negatively impact sexuality.
SD is not part of the normal aging process!!
It is a result of physical illness and environmental
and/or psychological factors.
– Sexual desire disorder (decreased libido)
– Sexual arousal disorder
– Orgasm disorder
– Sexual pain disorder
DSM IV – Diagnostic & Statistical Manual
of Mental Disorders
96
Shabsigh and Rowland, J Sex Med, 4(5) 2007; Clayton and Ramamurthy, Adv Psychosom Med, 29 2007
Sexuality & Sexual Dysfunction:
Unmet Need for Cancer Survivors
• SD affects 43% of women and 31% of men in the
United States
• SD is one of the more common enduring consequences
of cancer treatment and one that is not often addressed
• 73% of women with hematological malignancies
reported decreased libido, and 48% were dissatisfied
with their sex life
• Publications regarding SD in cancer patients are limited.
• Co-morbidities impact sexual function
97
Ganz & Greendale, J Natl Cancer Inst 2007; Tierny et al, Europ J Onc Nursing 2007
The Impact of Myeloma
Treatment on Sexuality
Immunomodulators
Thalidomide
Side Effects and
Clinical
Observations
Reported to induce
impotence in male
patients
Lenalidomide
• Unpublished reports
of erectile dysfunction
and decreased libido
–Sildenafil has
positive results in
restoring proper
functioning
Bortezomib
• Unpublished reports
of erectile dysfunction
and decreased libido
–Sildenafil has
positive results in
restoring proper
functioning
Our knowledge of the effects of novel myeloma
treatment on sexuality is very limited:
– Patients are reluctant to discuss the issue
– Sexuality assessments are not performed
98
Murphy and O’Donnell, Haematologica, 92 (10), 2007
Sexual Dysfunction:
Communication Is Critical!
• Urgent need for open communication between
physicians, nurses, and their patients
– Multiple well-established treatments for SD are
available for male and female patients.
• Patients may be unable or unwilling to verbalize this
as a side effect.
– This is often placed on the back burner, as treatment is most
important.
Ask your patients!!
99
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Sexual Dysfunction:
Assessing the Patient
Routine assessment is a powerful tool in identifying and
treating SD.
Permission to discuss
Give the patient permission to
initiate sexual discussion
Limited Information
Provide the limited information
needed to function sexually
Specific Suggestions
Give specific suggestions for
patients to proceed with sexual
relations
Intensive Therapy
Provide intensive therapy
surrounding the issues of
sexuality for patients
PLISSIT Assessment Model
100
Annon, The PLISSIT model: a proposed conceptual, 1976; Mick, Clin J Onc Nursing 2007
Interventions for Erectile Dysfunction
Interventions
Description
Precautions
Pharmacological Interventions
Phosphodiesterase type 5
inhibitors (sildenafil, vardenafil,
tadalafil)
Increase blood flow to the corpus
cavernosum
Vision problems, ischemic
neuropathy; refer to cardiologist!
Testosterone replacement
Increase testosterone levels
Urinary tract symptoms, apnea,
gynecomastia
Intercavernous vasoactive agents
Improve penile rigidity
Bleeding, infection, priapism,
penile acne, penile fibrosis
Non-Pharmacological Interventions
Vacuum Constriction Devices
Fill corpora cavernosa
Bruising, ischemia
Penile prosthesis
Silicone rods placed into the
corpora cavernosa
Permanent erection, rod breakage
Herbal Agents
Yohimbine
Penile vasodilation
Increased blood pressure and
heart rate
101
Aung et al, Am J Chin Med 2004; Bruner & Calvano, Nurs Clin North Am 2007
Sexual Dysfunction:
Position Statement
• Sexual dysfunction is a real issue in MM patients
• This condition is not fully discussed or addressed
comprehensively
• Oncology nurses can play a key role in bringing
this issue to the forefront with MM patients
• NLB to enact a plan of care that promotes
dialogue regarding the causes of sexual
dysfunction, and recommends assessment
practices to address this condition
102
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Strategic Recommendations
Sexual dysfunction is a real issue and is not fully
addressed in MM patients.
• Urgent need for open communications
– Physicians
– Nurses
– Patients
• Interventions
– Pharmacologic and non-pharmacologic
• Educational and psychosexual interventions
103
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Evidence-Based Recommendations
• Identify causative factors of sexual dysfunction
– Co-morbid conditions
– Secondary factors
– Tertiary factors
• Assess impact of MM treatment
• Evaluate sexual function (physical, lab)
– Effective communication
• Treatment of male and female sexual dysfunction
• Healthcare Provider Tool
• Patient Education Tool
104
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Impact of Myeloma Disease,
Treatments, Long-Term Effects and
Patient-Specific Characteristics on:
Health Maintenance
Elizabeth Bilotti, RN, MSN, APRN, BC
The John Theurer Cancer Center
at Hackensack University Medical Center
Hackensack, NJ
105
Optimizing Survival: Importance
of Health Maintenance
• Myeloma patients are expected
to live longer
• Good state of health provides
the opportunity to improve
survival by maintaining patients
on appropriate therapy
106
Impact of Novel Therapies
on Survivorship Care
• Unexpected new long-term
complications
• Second cancers
• Long-term maintenance for survivors:
quality of life
• Family/social problems
• Financial/insurance concerns
107
IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Barriers to Health Maintenance
• Low awareness among clinicians and patients about the
need to maintain overall wellness
• Lack of knowledge regarding existing guidelines
• Inadequate understanding about the role of comorbidities to poor patient health
• Time constraints
• Skepticism about the value of maintaining good health
• Unhealthy lifestyle choices
• Uninformed decisions
• Lack of health maintenance recommendations that
address the entire patient treatment spectrum
(ie, diagnosis through therapy)
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IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Health Maintenance:
Position Statement
• Overall health maintenance is vitally important to help MM
patients toward improved survival
• MM patients are facing multiple risks:
– Illnesses usually experienced by general
population of the same age
– Morbidities of MM itself
– Complications associated with MM treatments
• NLB to enact a plan of care that highlights
health maintenance for:
- Cardiovascular disease
- Secondary malignancies
- Endocrine disorders
- Bone metabolism disorders
- Sensory changes
- Depression
- Nutrition
- Chemical dependency
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Longo & Anderson, K. (2005). Plasma cell disorders. In Harrison's principle of internal medicine (16th ed., pp. 656-662).
New York: McGraw-Hill
Strategic Recommendations
Institute health maintenance as an integral part of the
MM patient care continuum.
• Personalize screening recommendations for health
promotion and disease prevention
• Disseminate the information to those who can effect
the most change:
– Patients
– Families
– Healthcare professionals
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IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Major Risk Factors Affecting
Health Maintenance
• Psychosocial
– Lifestyle choices
• Substance abuse
• Nutrition
• Activity
– Cognitive changes
• Depression
• “Chemo brain” effect
– Employability and access to healthcare
• Physical
– Dermatologic
• Skin cancer risk
– Altered immune system
• Immunizations
• Repeat hospitalizations
– Pain
– Anemia
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IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Evidence-Based Recommendations
• Current guidelines and their application for cancer patients
• Series of interventions offered to cancer patients at defined intervals
depending on:
– Age
– Gender
– Risk factors
• Specific needs of multiple myeloma patients due to novel therapeutics
• Sources for recommendations
– Centers for Disease Control and Prevention (CDC)
– US Preventative Services Task Force
– American College of Physicians
• Healthcare Provider Tool
• Patient Education Tool
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IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Specific Screening Interventions:
Examples
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IMF NLB Long-Term Care Survivorship Plan, manuscript in preparation
Closing Remarks
114
Why a Survivorship Care Plan for
Multiple Myeloma?
Increased survival leads to the
need for new approaches to
quality survivorship care.
115
Shifting Paradigm for
Survivorship Care: Nurse Role
Old Model
Survivorship as a stage:
• Decreasing contact
• Brief check-ups
• May not recognize survivorship
• Busy clinics
– Time constraints
– Focus on acutely ill
Emerging Model
Survivorship as a process:
• Contact along the extended continuum of care
• Survival plan will be developed shortly after diagnosis
• Survivors and families will be supported medically,
emotionally, financially.
• It is not just about IF and HOW LONG, but HOW WELL??
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Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007
Nurse-Led Survivorship Care
Nurses:
• Expert knowledge
• Close relationships with patients and families
• Understand psychosocial issues
• Recommend referral
• Work within a model of wellness promotion
rather than disease management
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Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007
Nurse-Led Survivorship Care (cont’d)
Barriers:
• Shortage of trained oncology nurses,
especially in outpatient settings
• Lack of coordinated care and communication
among healthcare providers
• Insurance and reimbursement issues
• Lack of appreciation/understanding of the role
of survivorship care with healthcare providers
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Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007
National Coalition for Cancer
Survivors (NCCS) “Imperatives”
NCCS’s “Imperatives for Quality Cancer Care: Access,
Advocacy, Action, and Accountability”:
• Nurses are major players
• Health promotion and wellness are critical in
survivor clinics
• Continued need for supportive care
• Critical value of education and rehabilitation for
symptoms:
– Fatigue, chronic pain, weight changes, decreased stamina
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NCCS. Imperatives for Quality Cancer Care: Access, Advocacy, Action, and Accountability, 1996
Focus of NLB Commitment
• Publication of the Survivorship Care Plan
will be immeasurably valuable to the general nursing
community involved in multiple myeloma patient
care
• Communication and dissemination of the
Survivorship Care Plan are important next steps
• Develop new educational materials/tools:
- Patient related
- Nurse related
120
Patient Education Tear-Out Tools
General format and clinical utility:
• Side effect description
• Novel therapies that may be associated
with the side effect
• Signs and symptoms
• Risk factors
• Healthcare provider recommendations
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NLB Consensus Statements, CJON June 2008
ASCO Tools for Survivorship Care
An important component of
survivorship care is a
patient’s treatment summary
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www.asco.org/treatmentsummary
IMF NLB Vision
for Survivorship Care
Survivorship care isn’t a stage!!!!
It is a continuum from diagnosis through the
patient’s life.
Prevention
Initial
treatment
Diagnosis
Continuing
care
Follow-up
Recurrence
Progressive
disease
Maintenance
Palliative care
Nurses are now empowered and enabled to
implement this vision
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Educational Resources
• International Myeloma Foundation
- IMF Myeloma Today Newsletter
- (800) 452-CURE (2873)
- www.myeloma.org
• Oncology Nursing Society
- www.ons.org
• American Cancer Society
• National Cancer Institute
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International Myeloma
Foundation
• Membership – more than 185,000 globally
• Scientific Advisory Board (72 world-recognized experts)
• Trained IMF Hotline Coordinators respond to more than 4,300
telephone calls and 3,600 e-mails each year.
• Multilingual Web site – in 2009 – tracking toward 70 million “hits” with a
97% repeat visitor rate
• The IMF distributes approximately 20,000 information packages (Info
Packs) a year. These packages are sent to patients, caregivers,
nurses, major cancer centers, clinics, and physician offices.
• Myeloma Minute
– Electronic informational e-mail
• Myeloma Manager – Personal Care Assistant
– A unique software solution engineered specifically for
myeloma patients
125
Acknowledgements
• Elizabeth Bilotti
• Beth Faiman
• Teresa Miceli
• Tiffany Richards
• Joseph Tariman
• Oncology Nursing Society
• International Myeloma Foundation
• Medical Education Resources
126
Question & Answer Session
Faculty Panel
127