Pomalidomide (CC4047) Plus Low-Dose Dexamethasone As Therapy for Relapsed Multiple Myeloma

Abstract

The combination of pomalidomide and low-dose dexamethasone is extremely active in the treatment of relapsed multiple myeloma, including high response rates in patients refractory to other novel agents.

A third-generation IMiD for MM

“…The rates of at least minimal response in the 4-mg and 2-mg cohorts were 49% and 43%, respectively, including VGPR and PR rates of 28.5% and 26%, respectively. These values of PR or better appear slightly lower than those observed in previously reported series of lenalidomiderefractory patients, 8,9 a finding that reflects the more heavily pretreated population of patients enrolled in the current trial and, importantly, their dual refractoriness to both lenalidomide and bortezomib. Consistent with this interpretation, similar rates of at least PR were seen in the phase 1 and 2 portions (the latter using daily pomalidomide at 4 mg on days 1-21 of 28-day cycles) of MM-002 study that included patients who had been previously treated with bortezomib and lenalidomide and were refractory to their most recent regimen.…”

“…Although a longer follow-up is required, the 6-month overall survival rates of 78% and 67% reported in the 2-mg and 4-mg cohorts are promising in a challenging population of patients for whom As in other pomalidomide trials, toxicity consisted primarily of myelosuppression, although it was more pronounced than what was previously reported with this agent. 8,9 Reduced hematopoiesis related to both advanced refractory disease and extensive prior treatments justifies the higher rates of grade 3-4 neutropenia (66% and 51% in the 4-and 2-mg cohorts, respectively) and thrombocytopenia (30.5% in both cohorts) observed in the current study compared with others. Nevertheless, the overall frequency of febrile neutropenia was low (0% and 11% in the 2-and 4-mg cohorts, respectively).…”

“…6,7 In two subsequent studies enrolling patients with rel/refr MM after 1 to 4 prior lines of treatment, including refractoriness to lenalidomide, salvage therapy with pomalidomide at 2 mg/day was given continuously in 28-day cycles combined with low-dose dexamethasone. 8,9 In one study, the overall rate of at least partial response (PR) was 63%, including 33% complete response or very good partial response (VGPR), and median progressionfree survival (PFS) was 11.6 months. 8 Among patients refractory to prior lenalidomide, PR or better was seen in the 32% to 40% range, suggesting a lack of cross-resistance between lenalidomide and pomalidomide.…”

“…8,9 In one study, the overall rate of at least partial response (PR) was 63%, including 33% complete response or very good partial response (VGPR), and median progressionfree survival (PFS) was 11.6 months. 8 Among patients refractory to prior lenalidomide, PR or better was seen in the 32% to 40% range, suggesting a lack of cross-resistance between lenalidomide and pomalidomide. 9 These promising results provided the basis of the study designed by Lacy et al to evaluate the efficacy of two different doses of pomalidomide in patients with dual refractoriness (defined as progression on therapy or within 2 months of stopping treatment) to lenalidomide and bortezomib.…”

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…Pomalidomide has significant activity in relapsed refractory myeloma, even in patients failing lenalidomide [114,115]. Response rate in patients refractory to lenalidomide and bortezomib is approximately 30% [116].…”