Pomalidomide/Dexamethasone/Ixazomib versus Pomalidomide/Dexamethasone for Patients with Relapsed/Refractory Multiple Myeloma: Results of Phase 1/2 Alliance A061202

Conference Correspondent - ASH 2015 - Multiple Myeloma

Pomalidomide in combination with dexamethasone is approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM); however, its progression-free survival prolongation is suboptimal in a lenalidomide- and bortezomib-refractory patient population. Ixazomib is a novel, oral proteasome inhibitor that has demonstrated single-agent activity as a single agent in RRMM and in combination with lenalidomide/dexamethasone in newly diagnosed patients. The phase 1/2 Alliance study A061202 sought to evaluate the safety and preliminary efficacy of the combination of ixazomib, pomalidomide, and dexamethasone versus pomalidomide and dexamethasone in patients with double-refractory multiple myeloma; Voorhees and colleagues reported on the phase 1 results of the study.1

In phase 1 of the study, using a 3+3 dose-escalation design, patients received pomalidomide (2?4 mg; days 1-21) plus ixazomib (3-4 mg; days 1, 8, and 15) and dexamethasone (40 mg; days 1, 8, 15, and 22) of a 28-day cycle on 4 dose cohorts. Of the 22 evaluable patients, all had received prior lenalidomide, bortezomib, and dexamethasone and 32% had received prior carfilzomib. Two dose-limiting toxicities of febrile neutropenia were reported, 1 each at dose levels 3 and 4. Grade 3/4 adverse events were hematologic, and included neutropenia, thrombocytopenia, anemia, thrombocytopenia, and lymphopenia; grade 3 infection was reported in 12% of patients. Treatment-related peripheral neuropathy occurred in 8 patients, and was ?grade 2 in severity. Dose reductions in at least 1 of the 3 drugs were reported in 50% of patients, whereas 50% experienced dose delays. To date, 2 patients have discontinued therapy due to adverse events; 1 due to grade 2 peripheral neuropathy and 1 due to grade 4 neutropenia. Of the 20 evaluable patients, the best overall response rate was 55%, including partial responses in 50% and very good partial response in 5%. Overall, these study results show encouraging preliminary efficacy with the combination of ixazomib, pomalidomide, and dexamethasone that is associated with an acceptable toxicity profile.

  1. Voorhees PM, et al. ASH 2015. Abstract 375.