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Copyright © 2010, Research To Practice, All rights reserved.
Part III: Multiple MyelomaMonday, October 4, 20107:30 PM - 8:30 PM ET
Monday Night with Research To Practice: An 8-Part Live CME Webcast Series
Kenneth C Anderson, MDKraft Family Professor of Medicine, Harvard Medical SchoolChief, Division of Hematologic NeoplasiaDirector, Jerome Lipper Multiple Myeloma CenterDirector, LeBow Institute for Myeloma TherapeuticsDana-Farber Cancer InstituteBoston, Massachusetts
Morie A Gertz, MDProfessor and ChairDepartment of MedicineMayo Clinic Rochester, Minnesota
Neil Love, MDModeratorResearch To PracticeMiami, Florida
Disclosures for Moderator Neil Love, MD
Dr Love is president and CEO of Research To Practice, which receives funds in the form of educational grants to develop CME activities from the following commercial interests: Abraxis BioScience, Allos Therapeutics, Amgen Inc, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cephalon Inc, Eisai Inc, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, Lilly USA LLC, Millennium Pharmaceuticals Inc, Myriad Genetics, Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Sanofi-Aventis and Spectrum Pharmaceuticals Inc.
Disclosures for Kenneth C Anderson, MD
N/A = Not Applicable
Advisory Committee and Consulting Agreements
Celgene Corporation, Millennium Pharmaceuticals Inc, Novartis Pharmaceuticals Corporation, Onyx Pharmaceuticals Inc.
Paid Research N/A
Speakers Bureau N/A
Disclosures for Morie A Gertz, MD
Advisory CommitteeCelgene Corporation, Eisai Inc, Millennium Pharmaceuticals Inc.
Paid Research N/A
Speakers Bureau N/A
N/A = Not Applicable
Copyright © 2010, Research To Practice, All rights reserved.
Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy in Patients With Newly Diagnosed Multiple Myeloma.Richardson PG et al. Blood 2010;116(5):679. Proc ASCO 2010;Ab 8016.
Lenalidomide Plus High-dose Dexamethasone Versus Lenalidomide Plus Low-dose Dexamethasone As Initial Therapy for Newly Diagnosed Multiple Myeloma: An Open-label Randomised Controlled Trial. Rajkumar SV et al. Lancet Oncol 2010;11(1):29.
Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Thalidomide, and Prednisone As Induction Therapy Followed by Maintenance Treatment With Bortezomib and Thalidomide Versus Bortezomib and Prednisone in Elderly Patients With Untreated Multiple Myeloma: A Randomised Trial. Mateos MV et al. Lancet Oncol 2010 Aug 24. [Epub ahead of print]. Optimising Bortezomib in Newly Diagnosed Multiple Myeloma.Rajkumar SV. Lancet Oncol 2010 Aug 24. [Epub ahead of print].
Copyright © 2010, Research To Practice, All rights reserved.
Lenalidomide Maintenance After Transplantation for MyelomaAttal M et al. Proc ASCO 2010;Ab 8018.
Phase III Intergroup Study of Lenalidomide Versus Placebo Maintenance Therapy Following Single Autologous Stem Cell Transplant (ASCT) for Multiple Myeloma (MM): CALGB 100104McCarthy PL et al. Proc ASCO 2010;Ab 8017.
Evaluating the Effects of Zoledronic Acid (ZOL) on Overall Survival (OS) in Patients (Pts) With Multiple Myeloma (MM): Results of the Medical Research Council (MRC) Myeloma IX StudyMorgan G et al. Proc ASCO 2010;Ab 8021.
Case History: Dr Anderson
• A 43-year-old woman is diagnosed with symptomatic IgA multiple myeloma
• Hb 8.0 g/dL• Albumin 3.5 g/dL• beta 2 microglobulin 3.0 mg/L
1) What is the stage of her disease?
34%
43%
23%
0% 10% 20% 30% 40% 50%
ISS Stage I
ISS Stage II
ISS Stage III
Copyright © 2010, Research To Practice, All rights reserved.
International Staging System for Multiple Myeloma
Greipp PR et alJ Clin Oncol 2005;23(15):3412-20.
International Staging System
ISS Stage CriterionMedian Survival
ISerum β2-microglobulin < 3.5mg/L
Serum albumin ≥ 3.5 g/dL62 months
II Neither Stage I nor Stage III 44 months
III Serum β2-microglobulin ≥ 5.5mg/L 29 months
Greipp PR et al. J Clin Oncol 2005 23(15):3412-20
2) What treatment, if any, would you recommend?
16%
5%
24%
16%
18%
13%
8%
0%
0% 5% 10% 15% 20% 25% 30%
None
TD (thalidomide-dexamethasone)
RD/Rd (lenalidomide-dexamethasone)
VD (bortezomib-dexamethasone)
VTD (bortezomib-thalidomide-dexamethasone)
RVD (lenalidomide-bortezomib-dexamethasone)
RVD melphalan and auto-transplant
RVD melphalan and auto-transplant lenalidomide maintenance
Has your approach to initial induction therapy for patients with MM who are eligible for transplant changed substantially in the past year?
47%
0% 10% 20% 30% 40% 50%
Percent responding
“Yes”
How has it changed?
I am using more triple-drug regimens 71%
I am using more bortezomib-based regimens 62%
I am using low-dose dexamethasone instead of high-dose dexamethasone as part of initial induction therapy
57%
I am using more lenalidomide-based regimens 38%
Other 6%
29%
26%
23%
7%
5%
2%
8%
0%
5%
10%
15%
20%
25%
30%
35%
Rd/RD RVD VD VdoxD TD VTD Other
Multiple Myeloma: First systemic treatment for patients deemed eligible for transplant by the treating oncologist (N = 128 patients)
National Patterns of Care Study, 2010, N = 43 medical oncologists
Copyright © 2010, Research To Practice, All rights reserved.
Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy in Patients with Newly Diagnosed Multiple Myeloma
Richardson PG et alBlood 2010;116(5):679-86.
≥ PR ≥ VGPR CR + nCR CR
All Patients ( N = 66) 100% 67% 39% 29%
Phase 2 Population ( N = 35) 100% 74% 57% 37%
Efficacy and Safety of RVD in Newly Diagnosed Myeloma
Richardson PG et al. Blood 2010;116(5):679-86.
Select Grade 3-4 Events with RVD
Sensory Neuropathy
Neuropathic Pain
Motor Neuropathy Neutropenia
Thrombo-cytopenia
Thrombo-embolism
2% 3% 2% 9% 6% 5%
Copyright © 2010, Research To Practice, All rights reserved.
Phase III Intergroup Study of Lenalidomide versus Placebo Maintenance Therapy Following Single Autologous Stem Cell Transplant (ASCT) for Multiple Myeloma (MM): CALGB 100104McCarthy PL et al Proc ASCO 2010;Abstract 8017.
Lenalidomide Maintenance After Transplantation for MyelomaAttal M et alProc ASCO 2010;Abstract 8018.
Lenalidomide (n = 210)
Placebo(n = 208) Hazard Ratio p-value
Time to Progression
Not Reached 25.5 months 0.42 <0.0001
McCarthy PL et al. Proc ASCO 2010;Abstract 8017.
Efficacy of Lenalidomide-Maintenance in Post-Transplant Setting
Lenalidomide (n = 307)
Placebo(n = 307) Hazard Ratio p-value
3-Year PFS 68% 34% 0.46 <0.0000001
Attal M et al. Proc ASCO 2010;Abstract 8018.
Erik Rupard, MDFort Gordon, GA
How would you manage a young patient with
MM, who achieves a good response with the
initial cycle of Rd, but tolerates Rd poorly
with profound nausea and fatigue. I have
seen a number of patients on Rd with
significant GI adverse events?
Copyright © 2010, Research To Practice, All rights reserved.
What about the effects of R on stem cell collections?
Richard Polkinghorn, MDBrunswick, ME
A 45-year old woman presents with
symptomatic myeloma and altered mental
status, and found to have increased
ammonia level without deranged liver
function. What is known about the
association between myeloma and
increased ammonia levels?
Case History: Dr Gertz
• A 79-year old woman is diagnosed with symptomatic IgA multiple myeloma
• Hb 10.6 g/dL
• Albumin 3.7 g/dL
• beta 2 microglobulin 3.2 mg/L
• Cytogenetics – Normal
• FISH t(11;14)
• Plasma Cell Labeling Index 0%
3) Would you consider this patient eligible for a transplant?
76%
24%
0% 10% 20% 30% 40% 50% 60% 70% 80%
Yes
No
Number of Patients Considered Eligible for Transplant In a Cross-Sectional Study from US Community Oncologists (N = 264 Patients)
National Patterns of Care Study, Research to Practice, 2010, N = 43 medical oncologists
≤45 50 55 60 65 70 75 80 85 ≥90
Yes (n = 128)No (n = 136)
6%
4%
13%
2%
47%
9%
19%
0%
0% 10% 20% 30% 40% 50%
Other
4) What treatment, if any, would you recommend?
CYBOR-D (cyclophosphamide-bortezomib-dex)
VD (bortezomib-dex)
V-PLD (bortezomib-PLD)
RD/Rd (lenalidomide-dex)
TD (thalidomide-dex)
VAD (vincristine-doxorubicin-dex)
MP (melphalan-prednisone)
22%21%
17% 17%
10%
2%
11%
0%
5%
10%
15%
20%
25%
VD Rd/RD MPT MPV MP RVD Other
Multiple Myeloma: First systemic treatment for patients deemed not eligible for transplant by the treating oncologist (N = 129 patients)
National Patterns of Care Study, 2010, N = 43 medical oncologists
Case History: Dr Gertz (continued)
• The patient is treated with lenalidomide plus dexamethasone
Copyright © 2010, Research To Practice, All rights reserved.
Lenalidomide plus High-Dose Dexamethasone versus Lenalidomide plus Low-Dose Dexamethasone as Initial Therapy for Newly Diagnosed Multiple Myeloma: An Open-Label Randomized Controlled Trial
Rajkumar SV et alLancet Oncology 2010;11(1):29-37.
RD (N = 223) Lenalidomide-
High Dose Dexamethasone
Rd (N = 222)Lenalidomide-
Low Dose Dexamethasone p-value
≥ PR ( by Cycle 4) 79% 68% 0.008
1-Year OS 87% 96% 0.0002
Grade 3-4 Adverse Events (by 4 Months)
52% 35% 0.0001
Deep Venous Thrombosis
26% 12% 0.0003
Grade 3-4 Infections
16% 9% 0.04
Safety and Efficacy Comparison of RD versus Rd
Rajkumar SV et al. Lancet Oncology 2010;11(1):29-37.
Copyright © 2010, Research To Practice, All rights reserved.
Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Thalidomide, and Prednisone As Induction Therapy Followed by Maintenance Treatment With Bortezomib and Thalidomide Versus Bortezomib and Prednisone in Elderly Patients With Untreated Multiple Myeloma: A Randomised TrialMateos MV et alLancet Oncol 2010 Aug 24. [Epub ahead of print].
Mateos MV et al. Lancet Oncol Aug 24. [Epub ahead of print].
Induction with VMP versus VTP Followed by Maintenance with VT versus VP for Untreated MM in Patients > 65 Years
Bortezomib (V): Induction phase, 1.3 mg/m2 twice weekly during a 6-weekfirst cycle, then weekly during subsequent cycles; maintenance phase, 1.3 mg/m2 twice weekly days 1, 4, 8 and 11 every 3 months
VMP(n = 130)
Maintenance
Induction VTP(n = 130)R1
R2R2
VT VP VT VP
VMP (N = 130)
VTP (N = 130) p-value
≥ PR 80% 81% 0.9
CR (immunofixation-negative) 20% 28% 0.2
Near CR (immunofixation-positive) 12% 8% 0.2
Partial response 48% 45% 0.7
Progression-free survival 34 mos 25 mos 0.1
Overall survival (3-year) 74% 65% 0.3
>Grade 3 Peripheral neuropathy 7% 9% 0.6
> Grade 3 Neutropenia 39% 22% 0.008
> Grade 3 Thrombocytopenia 27% 12% 0.0001
> Grade 3 Cardiac events 0 8% 0.001
Patients discontinuing due to SAEs 12% 17% 0.03
Safety and Efficacy of Induction VMP vs VTP
Mateos MV et al. Lancet Oncol Aug 24. [Epub ahead of print].
Copyright © 2010, Research To Practice, All rights reserved.
Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) Followed by Maintenance with Bortezomib and Thalidomide for Initial Treatment of Elderly Multiple Myeloma Patients
Palumbo A et alProc ASCO 2010;Abstract 8013.
VMP versus VMPT VT in Elderly Myeloma
VMP(n = 253)
VMPT VT(n = 250) p-value
≥ PR 81% 89% 0.01
CR 24% 38% 0.0008
3-Year PFS 40% 54% 0.006
3-Year OS 84% 86% 0.60
Palumbo A et al. Proc ASCO 2010;Abstract 8013.
*Three patients in twice weekly and one patient in once weekly group are not evaluable because they never began therapy.
NeuropathyVMP (Twice-weekly-
Bortezomib Schedule)VMP (Weekly-
Bortezomib Schedule)
All Grade (n = 63, 190*) 43% 21%
Grade 3 / 4 14% 2%
Should cytogenetics be obtained in all patients to stratify risk?
Copyright © 2010, Research To Practice, All rights reserved.
Evaluating the Effects of Zoledronic Acid (ZOL) on Overall Survival (OS) in Patients (Pts) With Multiple Myeloma (MM): Results of the Medical Research Council (MRC) Myeloma IX Study
Morgan G et al.
Proc ASCO 2010;Abstract 8021.
• Randomized to zoledronic acid versus clodronate, with treatment continued at least until disease progression
• ZOL significantly prolonged OS vs CLO (HR=0.84, p=0.0118)
— After adjustment for SREs (HR=0.85, p=0.0178)
• ZOL significantly reduced proportion of patients with SREs vs CLO (p=0.0004)
Morgan GJ et al. Proc ASCO 2010;Abstract 8021.
Improvement in Overall Survival with Zoledronic Acid (ZOL) in Patients with Newly Diagnosed Stage I-III Multiple Myeloma (N = 1,960)
Neil Fishbach, MDFairfield, CT
In view of the risk for osteonecrosis of
the jaw in patients receiving IV
bisphosphonates, is there a time or
role for spacing the administrations?
Copyright © 2010, Research To Practice, All rights reserved.
Is the depth of response as important in the non-transplant eligible patients as it is in the transplant eligible patients…or gentler, sequential approaches just as good or even preferred?
Margaret Deutsch, MDRaleigh, NC
For an elderly patient with myeloma, who
attains CR in a few cycles of VMP, is there a
role for maintenance bortezomib?
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