%0 Journal Article
%T Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma
%J -
%D 2019
%R https://doi.org/10.1038/s41408-019-0198-4
%X This phase I dose-escalation/expansion study evaluated isatuximab (anti-CD38 monoclonal antibody) monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Patients progressing on or after standard therapy received intravenous isatuximab (weekly [QW] or every 2 weeks [Q2W]). The primary objective was to determine the maximum tolerated dose (MTD) of isatuximab. Overall, 84 patients received£¿¡Ý£¿1 dose of isatuximab. The MTD was not reached; no cumulative adverse reactions were noted. The most frequent adverse events were infusion reactions (IRs), occurring in 37/73 patients (51%) following introduction of mandatory prophylaxis. IRs were mostly grade 1/2, occurred predominantly during Cycle 1, and led to treatment discontinuation in two patients. CD38 receptor occupancy reached a plateau of 80% with isatuximab 20£¿mg/kg (highest dose tested) and was associated with clinical response. In patients receiving isatuximab£¿¡Ý£¿10£¿mg/kg, overall response rate (ORR) was 23.8% (15/63), including one complete response. In high-risk patients treated with isatuximab 10£¿mg/kg (QW or Q2W), ORR was 16.7% (3/18). Median (range) duration of response at doses£¿¡Ý£¿10£¿mg/kg was 25 (8¨C30) weeks among high-risk patients versus 36 (6¨C85) weeks for other patients. In conclusion, isatuximab demonstrated a manageable safety profile and clinical activity in patients with RRMM
%U https://www.nature.com/articles/s41408-019-0198-4