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Elranatamab Induces Clinical and Molecular Responses in R/R MM

December 11, 2022

Mid-January 2023

Brandon May

Brandon May is a medical journalist based in Detroit.

Elranatamab induced durable clinical and molecular responses in patients with relapsed or refractory (R/R) multiple myeloma (MM), according to results of the MagnetisMM-1 trial presented at the 64th ASH Annual Meeting and Exposition. The ongoing phase I trial is investigating the safety, pharmacokinetics, pharmacodynamics, and efficacy of elranatamab in the R/R MM population.

“BCMA [B-cell maturation antigen] is a validated target in MM,” explained Noopur Raje, MD, of Harvard Medical School in Boston, who presented the findings. “Elranatmab is a humanized bispecific antibody targeting BCMA on myeloma cells and CD3 on T cells, inducing a selective cytotoxic T-cell response against myeloma cells.”

Patients with R/R MM (n=55) in the first-in-human trial received subcutaneous doses of elranatamab that ranged from 80 to 1,000 µg/kg. Treatment administration was weekly or every two weeks. The investigators assessed rates of treatment-emergent adverse events (TEAEs) and the incidence of cytokine release syndrome (CRS). Additionally, cytokines, pharmacokinetics, lymphocyte subsets, and soluble BCMA were evaluated over the course of the study.

In terms of efficacy, the researchers also assessed clinical response according to the criteria of the International Myeloma Working Group (IMWG) and measurable residual disease (MRD) status based on next-generation sequencing at a sensitivity of 1×10-5 aligned with the IMWG criteria.

At time of data cutoff in September 2022, all patients received a subcutaneous dose of elranatamab of at least 215 μg/kg. The median age of the cohort was 64 years, and more than a quarter of patients (27%) were Black/African American or Asian. This is encouraging, according to Dr. Raje, who said these demographics are “really reflective of what we see in the community.”

Patients received a median of five prior regimens. Most patients were triple class refractory (91%) and had previously received hematopoietic cell transplantation (69%). Nearly a third (29%) had high cytogenetic risk, and approximately 24% had previously received BCMA-targeted therapy.

Anemia, CRS, injection site reaction, lymphopenia, and neutropenia were the most common TEAEs. The incidence of CRS was 67% at the recommended elranatamab dose of 1,000 µg/kg or 76 mg, but these events were limited to grade 1 (33%) or 2 (33%). No grade 3 or higher CRS events were reported.

Treatment with the antibody therapy was associated with increased proliferation of peripheral T cells. Cytokines increased with the initial dose of the study therapy but were reduced by pre-medication. Additionally, soluble BCMA decreased with disease response.

“Looking at soluble BCMA levels is going to be something we’re going to need to use in practice,” Dr. Raje commented, “specifically when we start thinking about sequencing some of these drug products.”

The median time to response was 36 days. Over a median follow-up of 12.0 months, the observed objective response rate in only IMWG-confirmed responses was 64%, which included 56% of patients who achieved very good partial response (VGPR) or better and 38% of patients who achieved complete response (CR) or better.

All evaluable patients who had a confirmed CR or better achieved MRD negativity (sensitivity of 1×10-5), including two patients who had MRD negativity and continued stringent CR beyond a two-year period.

More than half of patients (54%) who previously received BCMA-directed therapy achieved response, including 46% of patients with a VGPR or better. The probability of being event-free at 12 months among responders was 59%. The estimated median duration of response in the heavily pretreated patient population was 17.1 months.

Limitations of the study included the small sample size as well as the lack of a control group.

Any conflicts of interest declared by the authors can be found in the original abstract.

Reference

Raje N, Bahlis NJ, Costello C, et al. Elranatamab, a BCMA targeted T-cell engaging bispecific antibody, induces durable clinical and molecular responses for patients with relapsed or refractory multiple myeloma. Abstract #158. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana.

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