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Lenalidomide in Newly Diagnosed Multiple Myeloma Clinical Update EHA 2010 DR. OUSSAMA JRADI

Lenalidomide in Newly Diagnosed Multiple Myeloma Clinical Update EHA 2010 DR. OUSSAMA JRADI. ASCO and EHA 2010 re-defined the Meaning of Maintenance Treatment in Multiple Myeloma.

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Lenalidomide in Newly Diagnosed Multiple Myeloma Clinical Update EHA 2010 DR. OUSSAMA JRADI

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  1. Lenalidomide in Newly Diagnosed Multiple Myeloma Clinical Update EHA 2010DR. OUSSAMA JRADI

  2. ASCO and EHA 2010 re-defined the Meaning of Maintenance Treatment in Multiple Myeloma • 3 major trials have demonstrated significant superiority of maintenance, utilizing lenalidomide in this setting.

  3. Is Longer Treatment Better?

  4. EHA 2010 – Yes, longer treatment is better in patients after autologous transplant!EHA 2010 – Yes longer treatment is better in elderly patients not eligible for transplant!

  5. Lenalidomide Maintenance after Autologous Transplantation for Myeloma: First Interim analysis of a prospective randomized study of the Intergroupe Francophone du Myélome (IFM 2005-02 trial) By Michel Attal, Gerald Marit, Denis Caillot, Thierry Facon, Philippe Moreau, Cyrille Hulin, Claire Mathiot, Hervé Avet-Loiseau, and Jean-Luc Harousseau. for the IFM

  6. IFM 2005-02: Study design Phase III randomized, placebo-controlled trial N= 614 patients, from 78 centers, enrolled between 7/2006 and 8/2008 Patients < 65 years, with non-progressive disease,  6 months after ASCT in first line Randomization: stratified according to Beta-2m, del13, VGPR Consolidation: Lenalidomidealone 25 mg/day p.o. days 1-21 of every 28 days for 2 months Arm A= Placebo (N=307)10-15 mg/d 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 Myelome.

  7. IFM 2005 02 Trial: Patient characteristics

  8. IFM 2005-02 : PFS from randomization .

  9. IFM 2005-02 : PFS from randomization Rev p<10-7 Placebo P < 10-7

  10. PFS according to Response Pre-Consolidation VGPR or CR PR or SD p<10-5 p=0.001 HR= 0.37 - CI 95% [0.25-0.58] HR= 0.54 - CI 95% [0.37-0.78]

  11. Grade 3-4 Adverse Events during Maintenance Definitive Discontinuation for SAE: placebo = 4% vs lenalidomide = 6% (NS)

  12. IFM 2005-02: First Interim Analysis (Cut off date 4th September 2009) • Maintenance therapy with Lenalidomide: • Is well tolerated: • Low discontinuation rate due to SAE (A=4%vs B=6%, NS) • No increased incidence of DVT or peripheral neuropathy • Is superior to placebo: • 54% reduction risk of progression (p < 10-7) • In all stratified subgroups (VGPR, ß2m, del 13) • A longer follow-up is required to appreciate the impact of Lenalidomide on OS (Final analysis: 8/2010)

  13. Lenalidomide Treatment of elderly patients with newly diagnosed MM with MPR followed by R maintenance

  14. N=459, 82 centers in Europe, Australia Phase III Study Schema Cycles (28-day) 1-9 Cycles 10+ MPR-R M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 R: 10 mg/day po, days 1-21 RANDOMISATION Diseaseprogression Lenalidomide (25 mg/day) +/- dexamethasone LenalidomideContinued Tx 10 mg/day,days 1-21 MPR M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 R: 10 mg/day po, days 1-21 Primary Comparison MPR-R vs. MP Placebo MP M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 PBO: days 1-21 Secondary Comparison MPR-R vs. MPR Addition of MPR arm per EMEA advice Placebo Double-Blind Treatment Phase Open-Label Extension/Follow-Up Phase Stratified by age (≤ 75 vs. > 75 years) and stage (ISS 1,2 vs. 3) 16 M, melphalan; P, prednisone; R, lenalidomide; PBO, placebo.

  15. Patient Characteristics • 459 patients randomised between Feb 2007 and Sept 2008 • 180 patients ongoing (MPR-R: 73; MPR: 54; MP: 53) ISS, International Staging System 17

  16. Best Response a. As measured using EBMT criteria1 b. Immunofixation negative with or without bone marrow confirmation c. VGPR: >90% reduction in M-protein 18 1. Bladé J et al. Br J Haematol. 1998;102:1115-1123.

  17. Progression-Free SurvivalSecond Interim Analysis58% Reduced Risk in PFS 1 0 0 1 0 0 Median PFS Not reached MPR-R 13.0 months 7 5 7 5 MP Median follow up: 21 mos Patients without Event (%) 5 0 5 0 2 5 HR 0.423 95% CI [0.330, 0.755] Logrank P<0.001 2 5 0 0 0 5 1 0 1 5 2 0 2 5 3 0 0 5 1 0 1 5 2 0 2 5 3 0 P P F F S S T T i i m m e e ( ( m m o o n n t t h h s s ) ) 19

  18. MPR-R vs. MPR Secondary Comparison Cycles (28-day) 1-9 Cycles 10+ MPR-R M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 R: 10 mg/day po, days 1-21 RANDOMISATION Diseaseprogression LenalidomideContinued Tx 10 mg/day,days 1-21 Primary Analysis MPR-R vs. MP MPR M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 R: 10 mg/day po, days 1-21 Placebo Secondary Comparison MPR-R vs. MPR Addition of MPR arm per EMEA advice Double-Blind Treatment Phase 22 M, melphalan; P, prednisone; R, lenalidomide; PBO, placebo.

  19. MPR-R vs. MPRLandmark PFS Analysis After Cycle 969% Reduced Risk in PFS 1 0 0 MPR-R MPR 7 5 Patients without Event (%) 5 0 2 5 HR 0.314 95% CI [0.126, 0.476] Logrank P<0.001 0 0 5 1 0 1 5 2 0 P F S T i m e ( m o n t h s ) 23

  20. Grade 3/4 AEs After Cycle 9 (Continuous Lenalidomide) • Overall toxicity in maintenance phase is rather low: Grade 3/4 < 5% 24 DVT, deep vein thrombosis

  21. ConclusionsMPR-R in Elderly NDMM Continuous lenalidomide is superior to regimens of limited duration MPR-R is superior to MP Higher and more rapid responses 50% reduced risk of progression Favorable safety profile Grade 4 neutropenia: 36% (febrile neutropenia: <7%) No Grade 3/4 peripheral neuropathy (Grade 2: 1% ) Low discontinuation due to AE: 16% MPR-R is a new standard treatment option for elderly patients 25

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