A Phase Ib study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma.

This phase Ib dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly [QW] for 4 weeks, followed by every 2 weeks [Q2W]), pomalidomide 4 mg (Days 1-21), and dexamethasone 40 mg (QW) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n=8], 10 [n=31], or 20 [n=6] mg/kg). Patients received a median of 3 (range 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 (42%) patients remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 TEAE was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pre-treated patients with RRMM. The 10 mg/kg QW/Q2W isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov: NCT02283775.