High Response Rates to Pomalidomide and Dexamethasone in Patients with Refractory Myeloma, Final Analysis of IFM 2009-02

The interim analysis of this phase 2 randomized open label trial was presented at ASH last year. It aimed to determine the impact of the combination of pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) in pts characterized with advanced myeloma (MM) following lenalidomide and bortezomib. The response rate (ORR, PR and better), and the median PFS were similar in the 2 arms, pomalidomide on days 1–21 vs. 1–28 of each 28-day cycle. The final analysis of IFM 2009-02 will be fully presented at ASH 2011. We have also studied subgroups characterized with refractory MM, in order to further demonstrate that the combination of pomalidomide and dexamethasone might benefit pts that have progressed after multiple novel agents.

This study was addressed to MM pts who had at best a stable disease with the last course of bortezomib and the last course of lenalidomide, or who were refractory to bortezomib and lenalidomide (as per IMWG criteria). The primary objective was ORR (PR and better). The responses were assessed centrally in Lille, and reviewed by an independent committee (all data reported herein are based on the IRC). FISH cytogenetic analysis was performed in Nantes on bone marrow plasma cells. All pts had received prophylaxis against venous thromboembolism. Data are presented for the overall population when there was no difference between the 2 arms. The analysis is performed on ITT.

Eighty four pts (57 male and 27 female) were enrolled; 43 in arm 21/28 and 41 in arm 28/28. The median (min-max) age was 60 (42–83) years. The median time from diagnosis to enrolment in IFM 2009-02 was 70.5 months (9–277). The median number of prior lines of therapy was 5 (1–13), and 100% of the pts had received bortezomib and lenalidomide as per protocol, 70% had received alkylating agents and 71% thalidomide. Overall, 21 (37.5%) pts had loss of 17p (n=15) or t(4;14) (n=6). At the cut-off of March 1^st 2011 the median follow-up for alive pts was 10.4 months (1.6–14.3), the median number of cycles administered was 8 (1–18) in arm 21/28 and 6 (1–18) in arm 28/28. The ORR was 34.9% in arm 21/28 and 34.1% in arm 28/28, including 4.7% and 7.3% VGPR, respectively. Overall, 40 (47.6%) pts had stable disease (including minor response) and 3 pts reached CR. The median (95%CI) PFS was 6.3 (4.1–9.1) months in either arm, and the median duration of response was 11.4 (3.7–13.6) months and 7.9 (4.0–) months in arm 21/28 and 28/28, respectively. The median PFS was 4.2 (3.3–6.9) months for pts with SD as compared to 12.6 (9.9–14.8) months in pts that had a response. A summary of subgroups characterized with refractory MM is presented in the table below. Survival and toxicity will be updated at ASH 2011.

Pomalidomide and dexamethasone is active and well tolerated in these heavily pre-treated MM pts. This study provides further evidence that pomalidomide has no-cross resistance with lenalidomide and suggests that it can provide benefit for pts who have relapsed after other novel therapies.

Leleu:LeoPharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Research Funding; Amgen: Honoraria; Novartis: Research Funding. Roussel:Celgène: Honoraria; Janssen: Honoraria. Hulin:Celgene: Honoraria; Janssen: Honoraria. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.