Response to Salvage Therapies and Outcome of Patients with Multiple Myeloma Relapsing After Pomalidomide Therapy

Pomalidomide is an immunomodulatory compound to be used for heavily pre-treated patients with relapse and refractory multiple myeloma and has shown considerable efficacy in recent clinical trials. It is not clear how patients may respond to other therapies, once the disease becomes refractory to pomalidomide. We examined this question among a cohort of patients receiving pomalidomide therapy in phase 2 clinical trials.

Patients enrolled in an ongoing phase 2 clinical trial of pomalidomide (2-4 mg daily) along with dexamethasone (40 mg weekly), in relapsed myeloma, form the study population. Several cohorts of patients (>= 3 prior therapies not specified, lenalidomide refractory, and lenalidomide and bortezomib refractory patients were enrolled sequentially in this trial (Lacy, M.Q., et al., J Clin Oncol, 2009. 27(30): p.5008–14). Only those patients who have gone off study for disease progression were included in the current analysis. Details of subsequent therapies and survival data were obtained from the medical records.

Forty-seven patients from among 142 patients enrolled on the clinical trial between November, 2007 and April, 2010 were included in the study. The median (range) duration of pomalidomide therapy was 4 (0.6-16) months. 15 (32%) patients were lenalidomide refractory and 11 (23%) were refractory to both lenalidomide and bortezomib at the time of study entry. The best confirmed response to pomalidomide was MR (Minimal Response) or better in 23 patients (52%). Various regimens were employed following relapse on pomalidomide. The response to the first regimen following relapse in the 34 patients where salvage therapy was initiated is as shown in Table 1. Overall, 81 regimens were employed across 34 patients; median (range) number of regimens per patients was 1 (0-8). The response rates to the different regimens were as shown in the Table 1. The median overall survival (OS) from the time of progression on pomalidomide was 14.7 months (95% CI; 4, NR). The OS was similar between those patients who had a response to pomalidomide (MR or better) and those who did not. However the OS was shorter for patients who were refractory to lenalidomide and bortezomib (2.1 months) compared to those who were lenalidomide refractory only (6.5 months), and the non-refractory group (NR), P=0.06.

This study confirms poor outcome of the patients relapsing after all available therapies. It also gives interesting insights into the activity of different regimens among patients who have relapsed after pomalidomide. The findings once again highlight the incurable nature of the disease and warrant further investigation to develop newer effective treatment regimens for this group of patients who presently do not have effective therapeutic options especially in the relapsed setting.

ASCT: Autologous Stem Cell Transplantation, Bz: Bortezomib, Mel=Melphalan, Dex: Dexamethasone, CRD: Cyclophosphamide, Revlimid (Lenalidomide), Dexamethasone, CTX; Cyclophosphamide, Len; Lenalidomide, Sor: Sorafenib, VDT-PACE: Velcade (Bortezomib), Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide.

SD; Stable Disease; Prog; Progression MR: Minimal Response; PR: Partial Response.

Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Mikhael:Celgene: Research Funding; Onyx: Research Funding; Novartis: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.