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Multiple Myeloma in Practice An Expert Commentary With Kenneth C. Anderson, MD A Clinical Context Report

Multiple Myeloma in Practice An Expert Commentary With Kenneth C. Anderson, MD A Clinical Context Report. Jointly Sponsored by: and. Clinical Context: Multiple Myeloma in Practice Expert Commentary. Clinical Context: Multiple Myeloma in Practice Expert Commentary.

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Multiple Myeloma in Practice An Expert Commentary With Kenneth C. Anderson, MD A Clinical Context Report

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  1. Multiple Myeloma in PracticeAn Expert Commentary With Kenneth C. Anderson, MDA Clinical Context Report

  2. Jointly Sponsored by: and Clinical Context: Multiple Myeloma in PracticeExpert Commentary

  3. Clinical Context: Multiple Myeloma in PracticeExpert Commentary Supported in part by an educational grant from Celgene Corporation.

  4. Multiple Myeloma in PracticeClinical Context Series The goal of this series is to provide up-to-date 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.

  5. Multiple Myeloma in PracticeClinical Context SeriesTarget Audience Hematologists, oncologists, primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of multiple myeloma.

  6. Activity Learning Objective Upon successful completion of this educational program, participants should be able to: • Review the relevance and significance of the activity in the broader context of clinical care

  7. CME Information: Physicians • Statement of Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Projects In Knowledge and MedPage Today. Projects In Knowledge is accredited by the ACCME to provide continuing medical education for physicians.

  8. CME Information • Credit Designation Projects In Knowledge designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity.

  9. CME Information: Physicians • Credit for Family Physicians MedPage Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, 2011. Term of approval is for one year from this date. Each article is approved for 0.5 Elective credits. Credit may be claimed for one year from the date of each article.

  10. CE Information: Nurses • Statement of Accreditation • Projects In Knowledge, Inc. (PIK) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. • Projects In Knowledge is also an approved provider by the California Board of Registered Nursing, Provider Number CEP-15227. • This activity is approved for 0.50 nursing contact hours. • There is no fee for this activity DISCLAIMER: Accreditation refers to educational content only and does not imply ANCC, CBRN, or PIK endorsement of any commercial product or service.

  11. CE Information: Pharmacists • Projects In Knowledge® is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been planned and implemented in accordance with the ACPE Criteria for Quality and Interpretive Guidelines. This activity is worth up to 0.5 contact hours (0.05 CEUs). The ACPE Universal Activity Number assigned to this knowledge-type activity is 0052-9999-11-1637-H04-P.

  12. Discussant Kenneth C. Anderson, MD Kraft Family Professor of MedicineDepartment of MedicineHarvard Medical SchoolAmerican Cancer Society Clinical Research ProfessorDirector, Jerome Lipper Multiple Myeloma CenterMedical OncologyDana-Farber Cancer InstituteBoston, Mass.

  13. 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.

  14. 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.

  15. Multiple Myeloma • Hematologic cancer of plasma cells in bone marrow • Dependent on bone microenvironment for growth, survival, and development of drug resistance

  16. 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

  17. 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

  18. FDA Approval (cont’d) • Lenalidomide (Revlimid) • 2006: Approved for relapsed multiple myeloma in combination with dexamethasone

  19. 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.

  20. Best Response to Treatment for the Treated Population (All Patients) Response* n % 90% CI CR 19 29 20-39 nCR 7 11 5-19 VGPR 18 27 18-38 PR 22 33 24-44 CR + nCR 26 39 29-50 CR + nCR + VGPR 44 67 56-76 At least PR 66 100 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. IFM 2005-02 -- Study Design Phase III randomized, placebo-controlled trialN=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.

  27. 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.

  28. 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.

  29. 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 micro-environment for growth, survival, and drug resistance

  30. 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)

  31. 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

  32. 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

  33. 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.

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