Isatuximab is an anti-CD38 monoclonal antibody with multiple mechanisms of action. This Ph1b open-label, multicenter study (NCT02283775) of isatuximab in combination with pomalidomide (pom) and dexamethasone (dex) for relapsed and refractory multiple myeloma (RRMM) had two parts; part A identified the recommended dose of 10 mg/kg of isatuximab using weight-based infusion volume in mg/hour (h) (J Clin Oncol 2018; 36 Suppl;3038).
To evaluate the feasibility and safety of a fixed volume infusion (rate in mL/h) of isatuximab (10 mg/kg) in combination with pom/dex in RRMM.
Patients (pts) with RRMM had received ≥2 prior lines including lenalidomide and a proteasome inhibitor (PI). Isatuximab 10 mg/kg was administered from a 250 mL fixed infusion volume. First infusion: initiated at 25 mL/h and increased gradually to 150 mL/h if no infusion reaction (IR). Second infusion: initiated at 50 mL/h, increased gradually up to 300 mL/h if no IR. Third and subsequent infusions: initiated at a fixed infusion rate of 200 mL/h until the total volume was infused. Standard prophylactic medication with antihistaminic and antipyretic agents without post-infusion corticosteroid prophylaxis was given. Primary endpoint: incidence of grade (GR) ≥3 IRs during the first 6 isatuximab infusions. Secondary endpoints included duration of infusion and safety. Statistical analyses are based on the all treated pts who had completed ≥6 isatuximab infusions or discontinued early by the preliminary analysis cut-off date of 02Jan2019.
Of 34 pts (all treated), 24 (70.6%) were still on treatment. Median age 64 years (range 46–85; majority [19/34, 55.9%] aged <65). All pts were previously treated with a PI and immunomodulatory drug. Median number of cycles was 3.5 with 32 (94.1%) pts having started at least 2 cycles (minimum 5 infusions) and 17 (50.0%) pts having started at least 4 cycles (minimum 9 infusions). Overall median duration of exposure was 13.4 weeks (range 1–37). Median relative dose intensities for isatuximab, pom, and dex were 94.8%, 85.9% and 91.1%, respectively. Median duration of infusion decreased from 3.94 h in first infusion to 1.25 h from third infusion onwards (table).
IRs (any GR) were reported in 16/34 (47.1%) pts and in 16/317 (5.0%) infusions. All IRs were GR2, only occurred during the first isatuximab infusion, and were handled through infusion interruption with pts recovering the same day. No delayed onset IRs occurred. Three (8.8%) pts discontinued due to treatment-emergent adverse events (2 severe infections; 1 sudden death) and GR≥3 infections were reported in 14.7%. GR4 neutropenia and GR4 thrombocytopenia were observed in 39.4% and 12.1% pts, respectively.
Isatuximab 10 mg/kg administered in a 250 mL fixed infusion volume with infusion rate in mL/h had a considerably shorter infusion time (median 75 minutes) compared with reported infusion schedule in mg/h (median 174 minutes) for third and subsequent infusions. IRs after the first infusion or IRs with delayed onset were not reported. The general safety profile of the simplified infusion was manageable and consistent with previous observations for this combination of isatuximab with pom and dex.