Jeffrey A. Zonder, MD, hematologist-oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, discusses data from the first-in-human study testing REGN5458 as a monotherapy for relapsed/refractory multiple myeloma patients (NCT03761108). Data from the phase 1 portion of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Zonder explains, REGN5458 is a BCMA x CD3 bispecific antibody that is currently being investigated in a phase 1/2 clinical trial. Data presented at ASH 2021 was related to the phase 1 portion of this study which is assessing the safety, tolerability, and dose-limiting toxicities (DLTs) of REGN5458 in patients with relapsed/refractory multiple myeloma as well as determining a recommended phase 2 dose regimen.

As of data cut-off (June 10, 2021), 68 patients were treated with REGN5458 in the dose escalation cohort with full doses ranging from 3–400 mg. Patients had a median of 5 prior lines of systemic therapy and the median duration of follow-up was 2.4 months. 

Treatment-emergent adverse events (TEAE) were reported in 66 patients (97.1%), and Grade 3 or more TEAEs were reported in 52 (76.5%) patients. The most frequent TEAEs were fatigue in 29 patients (42.6%), and cytokine release syndrome (CRS) in 26 patients (38.2%). No patient had Grade 3 or more CRS or discontinued treatment due to CRS. There were no Grade 3 or more neurotoxicity events. 

As Dr. Zonder notes, responses were observed at all dose levels and a maximally-tolerated dose was not reached at any level. Amongst patients treated at the 96 and 200 mg dose levels, the response rate was 73.3%. Across all dose levels, 92.6% of all responders achieved at least a very good partial response and 48.1% of responders had a complete response (CR) or stringent CR. Patients without extramedullary plasmacytomas responded more frequently than those with them. The Kaplan–Meier estimated median duration of response was not reached. The probability of duration of response ≥8 months was 92.1% with responses ongoing up to 19 months at the latest data cut-off.

Overall, REGN5458 continues to show an acceptable safety and tolerability profile as well as promising durable responses in triple- to penta-refractory patients with relapsed/refractory multiple myeloma. 

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