Multiple Myeloma in Practice
An Expert Commentary With
Kenneth C. Anderson, MD
A Clinical Context Report
Clinical Context: Multiple Myeloma in Practice
Expert Commentary
Jointly Sponsored by:
and
Clinical Context: Multiple Myeloma in Practice
Expert Commentary
Supported in part by an educational grant from
Celgene Corporation.
Multiple Myeloma in Practice
Clinical Context Series
The goal of this series is to provide up-todate information and multiple perspectives
on the pathogenesis, patient identification,
symptoms, risk factors, and current and
emerging treatments and best practices in
the management of multiple myeloma.
Multiple Myeloma in Practice
Clinical Context Series
Target Audience
Hematologists, oncologists, primary care
physicians, nurses, nurse practitioners,
physician assistants, pharmacists, and
other healthcare professionals involved in
the management of multiple myeloma.
Activity Learning Objective
CME Information: Physicians

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Discussant
Kenneth C. Anderson, MD
Kraft Family Professor of Medicine
Department of Medicine
Harvard Medical School
American Cancer Society Clinical Research Professor
Director, Jerome Lipper Multiple Myeloma Center
Medical Oncology
Dana-Farber Cancer Institute
Boston, Mass.
Disclosure Information
Kenneth C. Anderson, MD,
disclosed the following relevant financial
relationships: Served as an adviser or consultant for
Bristol-Myers Squibb; Celgene Corporation;
Millennium Pharmaceuticals, Inc; Merck & Co., Inc;
Novartis Pharmaceuticals Corporation;
Onyx Pharmaceuticals, Inc.
Disclosure Information
Vandana G. Abramson, MD, Assistant Professor of
Medicine, Vanderbilt University School of Medicine,
Nashville, Tenn.; Crystal Phend; and Dorothy Caputo, MA,
RN, BC-ADM, CDE, Nurse Planner, have disclosed that they
have no relevant financial relationships or conflicts of interest
with commercial interests related directly or indirectly to this
educational activity.
The staff of Projects In Knowledge and MedPage Today
have no relevant financial relationships or conflicts of interest
with commercial interests related directly or indirectly to this
educational activity.
Multiple Myeloma
• Hematologic cancer of plasma cells in bone
marrow
• Dependent on bone microenvironment for
growth, survival, and development of drug
resistance
FDA Approval
• Thalidomide (Thalomid)

1998: Approved under restricted access
program for treatment of skin lesions caused
by leprosy, studied under off-label
compassionate use in relapsed multiple
myeloma

2006: Approved for newly diagnosed multiple
myeloma in combination with dexamethasone
FDA Approval (cont’d)
• Bortezomib (Velcade)

2003: Accelerated approval for multiple
myeloma progressive after prior treatment

2005: Approved in multiple myeloma for
patients who received at least one prior
therapy

2008: Approved as initial therapy for multiple
myeloma
FDA Approval (cont’d)
• Lenalidomide (Revlimid)

2006: Approved for relapsed multiple
myeloma in combination with
dexamethasone
Phase I/II Study of Bortezomib, Lenalidomide,
and Dexamethasone Combination for Newly
Diagnosed Multiple Myeloma
• Best dose regimen consisted of three-week
cycles of:

Lenalidomide 25 mg on days 1 to 14

Bortezomib 1.3 mg/m2 on days 1, 4, 8, 11

Dexamethasone 20 mg on days 1, 2, 4, 5,
8, 9, 11, 12
Source: Richardson PG, et al Blood 2010; 116: 679-686.
Best Response to Treatment for the Treated
Population (All Patients)
Response*
CR
nCR
VGPR
PR
CR + nCR
CR + nCR + VGPR
At least PR
n
%
90% CI
19
7
18
22
26
44
66
29
11
27
33
39
67
100
20-39
5-19
18-38
24-44
29-50
56-76
96-100
CI indicates confidence interval; CR, complete response; nCR, near-complete response; PR,
partial response; VGPR, very good partial response.
*Per European Group for Blood and Marrow Transplant criteria, all response categories,
including VGPR, required a confirmatory assessment at 6 weeks.
Source: Richardson PG, et al Blood 2010; 116: 679-686.
Cancer and Leukemia Group B (CALGB)
Trial 100104 -- Overview
• Lenalidomide versus placebo as maintenance
therapy after a single autologous stem cell
transplantation
• Stage I to III multiple myeloma patient
population
Source: McCarthy PL, et al ASH 2010; Abstract 37.
CALGB Trial 100104 -- Overview (cont’d)
• Starting dose 10 mg/day, escalated to
15 mg/day after three months and
continued until disease progression
• Unpublished phase III data presented at
American Society of Hematology meeting
December 2010
Source: McCarthy PL, et al ASH 2010; Abstract 37.
CALGB Trial 100104 -- Results
• 60% reduction in risk of progression or death
with lenalidomide maintenance therapy after a
median follow-up of 17.5 months

46 of 231 patients on lenalidomide died or had
disease progression

96 of 229 patients on placebo died or had
disease progression

Statistically significant difference in favor of
lenalidomide at P<0.0001
Source: McCarthy PL, et al ASH 2010; Abstract 37.
CALGB Trial 100104 -- Adverse Events
• 15 secondary malignancies in the
lenalidomide maintenance group

3 cases of myelodysplastic syndrome/
acute myeloid leukemia
• 6 secondary malignancies the placebo group
Source: McCarthy PL, et al ASH 2010; Abstract 37.
Intergroupe Francophone du Myélome (IFM)
2005-02 Trial -- Overview
• Maintenance treatment with lenalidomide after
stem cell transplantation for multiple myeloma
• Phase III randomized, placebo-controlled trial
in 614 patients with non-progressive disease
• Unpublished final analysis data presented at
American Society of Hematology meeting Dec.
2010
Source: Attal M, et al ASH 2010; Abstract 310.
IFM 2005-02 -- Study Design
Phase III randomized, placebo-controlled trial
N=614 patients from 78 centers, enrolled Jul 2006 to Aug 2008
Patients <65 years, with non-progressive disease, ≤6 months
after ASCT in first line
Randomization: stratified according to Beta-2m, del13, VGPR
Consolidation: Lenalidomide alone
25 mg/day po days 1-21 of every 28 days for 2 months
Arm A = Placebo
(N=307) until relapse
Arm B = Lenalidomide
(N=307) 10-15 mg/d until relapse
Primary end-point: PFS.
Secondary end-points: CR rate, TTP, OS, feasibility of long-term lenalidomide
ASCT, autologous stem cell transplant; IFM, Intergroupe Francophone du Myélome
Source: Attal M, et al ASH 2010; Abstract 310.
IFM 2005-02 Trial -- Results
• Near doubling in progression-free survival

Median 42 months with lenalidomide
maintenance versus 24 months with placebo

60% on lenalidomide versus 33% on placebo
alive without progression at three years
Source: Attal M et al. ASH 2010; Abstract 310.
IFM 2005-02 Trial -- Results (cont’d)
• More secondary malignancies

16 with lenalidomide (10 hematologic)

3 with placebo
Source: Attal M et al. ASH 2010; Abstract 310.
Summary
At the end of this activity, participants should understand:

Multiple myeloma is a cancer of the plasma
cells in the bone marrow dependent upon
signals from the bone marrow microenvironment for growth, survival, and drug
resistance
Summary

Therapy has been dramatically advanced since
the late 1990s, with the introduction of:
– Thalidomide (Thalomid) for multiple myeloma
resistant to conventional therapies
– The proteasome inhibitor bortezomib (Velcade)
– The second-generation immunomodulatory
drug lenalidomide (Revlimid)
Summary

Triple drug therapy is the standard of care in
multiple myeloma, but combinations appear
more effective the earlier in the disease course
they are used

The combination of bortezomib, lenalidomide,
and dexamethasone for newly diagnosed
cases achieved a 100% response rate in one
study with 57% of patients getting a complete
or near complete response
Summary

Saving the better combinations until later in
the disease course may compromise their
efficacy as drug resistance may develop

Maintenance therapy with lenalidomide
improved progression-free survival 60%
compared with placebo in the CALGB trial
100104 and nearly doubled survival without
progression in the IMF 2005-02 trial
Summary

Lenalidomide maintenance therapy was
associated with excess secondary cancers in
the CALGB 100104 and IMF 2005-02 trials,
though the risk-benefit ratio may still favor the
treatment

Genetics may hold the key to biomarkers that
could aid in personalizing drug combinations
for multiple myeloma patients.