Meta analysis of overall survival in three multiple myeloma studies following Revlimid (lenalidomide) maintenance treatment.-Celgene.

Celgene Corporation announced data from a meta-analysis of overall survival in multiple myeloma (MM) patients receiving investigational maintenance treatment with Revlimid (lenalidomide) capsules following high-dose melphalan and autologous stem cell transplant (ASCT) were presented during the 52nd ASCO Annual Meeting in Chicago, Illinois . The analysis, based on data from studies conducted by the Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) with support from the National Cancer Institute , Intergroupe Francophone du Myélome (IFM) and the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), was presented by Dr. Philip McCarthy of Roswell Park Cancer Institute and lead investigator of the CALGB (Alliance) 100104 study.

The findings demonstrated significantly prolonged overall survival (OS) compared to the control arm of placebo or no maintenance. A meta-analysis of patient-level data from 1,209 patients in three randomized, controlled phase III studies (CALGB (Alliance) 100104, IFM 2005-02, GIMEMA-RVMM-PI-209) was conducted comparing lenalidomide maintenance (n=605) to either placebo or no maintenance (n=604). Each of these studies had individually shown that investigational lenalidomide maintenance treatment following autologous stem cell transplant reduced the risk of disease progression or death (PFS), the primary endpoint, by approximately 50% (McCarthy NEJM 2012; Attal NEJM 2012; Palumbo NEJM 2014). Results of this analysis showed that at a median follow-up of 80 months, the median overall survival had not been reached for patients receiving lenalidomide maintenance compared with 86 months for the control arm [95% CI: HR 0.74 (0.62-0.89); p=0.001], representing an estimated 2.5-year benefit in favor of lenalidomide maintenance. Hazard ratios for each of the three studies favored maintenance treatment with lenalidomide.

While not individually powered to evaluate this endpoint, each study contributed to the pooled OS benefit observed in the meta-analysis. The risk of developing a hematologic second primary malignancy (SPM) in the lenalidomide arm in the pooled analysis had a hazard ratio of 2.03 (95% CI: 1.14-3.61). The risk of developing a solid tumor SPM in the lenalidomide arm had a hazard ratio of 1.71 (95% CI: 1.04-2.79). Hematologic SPMs observed in the studies totaled 15 for the lenalidomide arm and eight for the control arm in CALGB (Alliance) 100104, 21 for lenalidomide and nine for control in IFM 2005-02, and none for either arm in the GIMEMA-RVMM-PI-209 study. Solid tumor SPMs observed in the studies totaled 17 for the lenalidomide arm and 10 for the control arm in CALGB (Alliance) 100104, 21 for lenalidomide and 13 for control in IFM 2005-02, and five for lenalidomide and two for the control arm in the GIMEMA-RVMM-PI-209 study.

Comment:Revlimid is not indicated for maintenance treatment following autologous stem cell transplant.