Promising results of elranatamab for MM in phase 2 MagnetisMM-3 trial 

Elranatamab displayed a manageable safety profile in patients with relapsed/refractory multiple myeloma (MM) in the phase 2 MagnetisMM-3 trial. Furthermore, the investigational agent demonstrated promising efficacy data, supporting the continued investigation of elranatamab.

Elranatamab is a humanised, bispecific antibody targeting BCMA-expressing MM cells and CD3-expressing T cells [1]. The MagnetisMM-3 study (NCT04649359) tested this agent in 187 patients with relapsed/refractory MM across 2 cohorts [2]. Prof. Nizar Bahlis (University of Calgary, Canada) presented the results of cohort A, including a patient population that had no prior exposure to BCMA-directed therapy (n=123). Notably, 96.7% of the participants were triple-class refractory at baseline. After 2 step-up doses of 12 mg and 32 mg respectively, the participants received 76 mg elranatamab once weekly, subcutaneously administered. The primary endpoint was the objective response rate (ORR) per blinded independent central review.

The confirmed ORR was 61.0%. In addition, 55.3% of the participants had at least a very good partial response and 27.6% had a complete or stringent complete response. Moreover, among participants who reached an objective response, the median time to response was 1.2 months. The median progression-free survival and overall survival had not been reached after 10.4 months of follow-up.

According to Prof. Bahlis, the safety profile of elranatamab was manageable. Haematologic events were the most common grade 3 or 4 treatment-emergent adverse events: anaemia (36.6%), neutropenia (48.0%), thrombocytopenia (22.0%), and lymphopenia (24.4%). Furthermore, cytokine release syndrome (CRS) occurred in 57.7% of the participants, with all of these events being of grade 1 or 2 severity. Prof. Bahlis added that the step-up priming regimen that was applied in this study mitigated the rate and severity of CRS. Finally, infections were seen in 66.7% of the participants, 35.0% being grade 3 or 4 infections.

So, in the phase 2 MagnetisMM-3 trial, elranatamab was well tolerated and efficacious in patients with relapsed/refractory MM, supporting the further investigation of this agent as monotherapy or in combination with other agents. The phase 3 MagnetisMM-5 trial (NCT05020236) evaluates elranatamab in relapsed/refractory MM and the phase 3 MagnetisMM-7 study (NCT05317416) tests elranatamab in patients with newly diagnosed MM as a post-transplant maintenance therapy.

1. Shah N, et al. Leukemia. 2020;34:985–1005.
2. Bahlis N, et al. Efficacy and Safety of Elranatamab in Patients with Relapsed/Refractory Multiple Myeloma Naïve to B-Cell Maturation Antigen (BCMA)-Directed Therapies: Results from Cohort a of the Magnetismm-3 Study. Abstract 159, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 202318 March 2024