Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma

Abstract

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1–8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.

Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab

“…Of the 6 participants for whom the response could be evaluated, 3 experienced a minimal response (MR) or better. 53 Another small case series consisting of 9 patients also demonstrated encouraging results for Isa-Pd after daratumumab therapy, with 7 patients showing a MR or better. 54 Mikhael et al reported the effect of single-agent isatuximab in patients who developed daratumumab resistance.…”

Anti CD38 monoclonal antibodies for multiple myeloma treatment

“…The primary endpoint for Part B was the incidence of Grade (Gr) ≥3 infusion reactions (IRs) during the first six Isatuximab infusions. 64 Forty-seven patients were enrolled. The median duration of exposure was 36.9 weeks.…”

“…The ORR in all subjects on Part B was 53.2% and 62.2% in Part A, with similar VGPR and CR rates (23.4% and 4.3% in Part B versus 22.2% and 2.2% in Part A, respectively). 64 In another phase Ib study, Isatuximab was combined with Carfilzomib (K) and dexamethasone in 33 RRMM. 65 Patients were previously treated with a median of three lines.…”

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

“…To decrease infusion times, numerous trials have confirmed that rapid infusion of daratumumab 90 min and isatuximab 70 min can be initiated safely following evidence of tolerability during the first cycle ( Table 3 ). 23 – 29 …”

“…In those patients treated with isatuximab, we utilize a similar prophylactic approach, though montelukast is not included and use of an H2 blocker is continued over the course of treatment. 29 …”