San Miguel JF et al. 1 Proc EHA 2013;Abstract S1151.

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Presentation transcript:

San Miguel JF et al. 1 Proc EHA 2013;Abstract S1151. Efficacy, Safety, and QoL in MM-003, a Phase 3, Multicenter, Randomized, Open-Label Study of Pomalidomide (POM) + Low-Dose Dexamethasone (LoDEX) vs High-Dose Dexamethasone (HiDEX) in RRMM1 MM-003: A Phase III, Multicenter, Randomized, Open-Label Study of Pomalidomide (POM) plus Low-Dose Dexamethasone (LoDEX) versus High-Dose Dexamethasone (HiDEX) in Relapsed/Refractory Multiple Myeloma (RRMM)2 San Miguel JF et al. 1 Proc EHA 2013;Abstract S1151. 2 Proc ASCO 2013;Abstract 8510.

Background Patients with RRMM with disease progression after treatment with bortezomib (Btz) and lenalidomide (Len) or thalidomide have a poor prognosis with a short overall survival (OS) and reduced quality of life. HiDEX is an established treatment for RRMM. POM demonstrated efficacy in patients with RRMM after Len and/or Btz therapy (Blood 2013;121:1968). Recently, pomalidomide (POM) was FDA approved for the treatment of MM in patients who have received ≥2 prior therapies, including Len and Btz, and have experienced disease progression within 60 days of their last therapy. Study objective: To determine the efficacy and safety of POM + LoDEX versus HiDEX in advanced RRMM. San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Phase III MM-003 Trial Design 28-d cycles until PD Eligibility (n = 455) Advanced relapsed MM or RRMM ≥2 prior lines of therapy Failure of Len and Btz No resistance to HiDEX in last line of therapy No Grade ≥2 PN POM + LoDEX (n = 302) POM: 4 mg, d1-21 LoDEX: 20 mg or 40 mg*, d1,8,15,22 R HiDEX (n = 153) HiDEX: 20 mg or 40 mg*, d1-4, 9-12, 17-20 PN = peripheral neuropathy * LoDEX or HiDEX: 20 mg (>75 years) or 40 mg (≤75 years) Thromboprophylaxis with lose-dose aspirin, low-molecular-weight heparin or equivalent was required for all patients receiving POM and those at high risk of thromboembolic events Primary endpoint: Progression-free survival (PFS) San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Proportion of Patients Progression-Free Survival (mos) PFS — Intention-to-Treat (ITT) Population (Median Follow-Up: 10 Months) 1.0 0.8 0.6 0.4 0.2 0.0 Median PFS POM + LoDEX (N = 302) 4.0 mos HiDEX (N = 153) 1.9 mos HR = 0.48 P < 0.001 Proportion of Patients 4 8 12 16 Progression-Free Survival (mos) With permission from San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

OS — ITT Population (Median Follow-Up: 10 Months) 1.0 0.8 0.6 0.4 0.2 0.0 Median OS POM + LoDEX (N = 302) 12.7 mos HiDEX (N = 153) 8.1 mos HR = 0.74 P = 0.028 Proportion of Patients 4 8 12 16 20 Overall Survival (mos) Nearly 50% of patients (n = 76) on the HiDEX arm received POM With permission from San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Subgroup Analyses of PFS and OS (POM + LoDEX vs HiDEX) HR PFS OS ITT population (n = 302, 153) 0.48 0.74 Len and Btz refractory (n = 225, 113) 0.52 0.77 Len as last prior Tx (n = 85, 49) 0.38 0.53 Btz as last prior Tx (n = 132, 66) 0.87 HR <1.0 favors POM + LoDEX San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Response Rates: ITT Population POM + LoDEX (n = 302) HiDEX (n = 153) p-value ORR 31% 10% <0.001 ≥VGPR 6% 1% — sCR/CR 0% ≥MR 39% 16% ≥SD 82% 61% ORR = overall response rate; VGPR = very good partial response; CR = complete response; sCR = stringent CR; MR = minimal response; SD = stable disease PFS of ≥MR with POM + LoDEX: 8 months San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Response Rates by Last Prior Therapy for Patients in the POM + LoDEX Arm 50 40 30 20 10 PR ≥ VGPR ≥ PR 34% ≥ PR 33% ≥ PR 30% ≥ PR 30% ≥ PR 28% 7 5 6 Patients (%) 5 5 28 27 25 25 24 Refractory to: BORT LEN BORT and LEN BORT as Last Prior Tx LEN as Last Prior Tx Response rate was consistent among all subgroups, including patients who received Len or Btz as last prior therapy. With permission from San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Grade 3 or 4 Adverse Events POM + LoDEX (n = 300) HiDEX (n = 150) Neutropenia Febrile neutropenia 48% 9% 16% 0% Anemia 33% 37% Thrombocytopenia 22% 26% Infections Pneumonia 30% 13% 24% 8% Bone pain 7% 5% DVT/PE 1% 0% Peripheral neuropathy DVT/PE = deep vein thrombosis/pulmonary embolism San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Health-Related Quality of Life (HRQoL): Changes Over Time POM + LoDEX HiDEX Improved 100 80 60 40 20 100 80 60 40 20 100 80 60 40 20 Global Health Status Physical Functioning Emotional Functioning Mean Score Worsened 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Treatment Cycle Treatment Cycle Treatment Cycle Increased 100 80 60 40 20 100 80 60 40 20 Pain Fatigue * Mean Score Decreased 1 2 3 4 5 1 2 3 4 5 Treatment Cycle Treatment Cycle POM + LoDEX consistently improved HRQoL measurements vs HiDEX Improved in physical functioning and decreased pain and fatigue * P < .05 With permission from San Miguel JF et al. Proc EHA 2013;Abstract S1151.

Author Conclusions Updated analyses reconfirm the advantage of POM + LoDEX compared to HiDEX despite 50% of patients in the HiDEX arm receiving subsequent POM. POM + LoDEX significantly improved PFS and OS compared to HiDEX. The benefit of POM + LoDEX was maintained regardless of refractoriness to Btz and Len, even as last prior treatment. The safety profile of POM + LoDEX is predictable and manageable. POM + LoDEX is generally well tolerated in patients with heavily pretreated RRMM. POM + LoDEX consistently improved HRQoL versus HiDEX for patients with heavily pretreated RRMM who had fully benefited from Btz and Len. In light of the OS advantage, POM + LoDEX, an oral treatment option, should be considered a new standard approach for patients with RRMM. San Miguel JF et al. Proc EHA 2013;Abstract S1151; Proc ASCO 2013;Abstract 8510.

Investigator Commentary: Phase III MM-003 Study of POM + LoDEX versus HiDEX for Patients with Advanced RRMM POM is an excellent way to continue therapy with an immunomodulatory agent after Len. Therapy for patients who have developed Len- refractory disease should be switched to POM. This may represent an extension phase, maintaining disease remission for 30% to 50% of patients. POM should not be administered at the end stage of myeloma treatment because it is less effective then. For end-stage MM, POM yielded a median PFS of 4 months versus 2 months with HiDEX in the Phase III MM-003 study. I am sure that if POM had been used immediately after Len, after first relapse, the median PFS might have been prolonged to 6 or 8 months. Additionally, the study resulted in a median OS of about 13 months with POM versus 8 months with HiDEX. The combination of POM with LoDEX improved the quality of life for patients with relapsed or refractory MM. Interview with Antonio Palumbo, MD, August 12, 2013