Understanding Adverse Events With BCMA-, Non-BCMA-Targeting Bispecific Antibodies in Multiple Myeloma

Both B-cell maturation antigen (BCMA)- and non-BCMA-targeting bispecific antibody therapies are associated with adverse events in multiple myeloma therapy, according to a poster presented at the 65th ASH Annual Meeting and Exposition.1 Understanding these adverse events is crucial when selecting a treatment and mitigating adverse events to optimize patient outcomes.

Investigators from the Taussig Cancer Institute at the Cleveland Clinic and at Kansas State University in Olathe, Kansas, conducted a pooled analysis of currently available literature on bispecific antibodies—including teclistamab, elranatamab, REGN-5458, AMG420, AMG701, CC-93269, TNB-383B, linvoseltamab, talquetamab, and cevostamab—published through June 2023. Safety data, including data around cytokine release syndrome, neurotoxicity, infection rate, and hematologic toxicities, were also collected by researchers.

The analysis included a total of 1926 patients (median age, 63 years; 5 previous lines of therapy) with relapsed/refractory multiple myeloma treated with bispecific antibodies. Within this group, 66.7% were treated with a B-cell maturation antigen (BCMA)-directed bispecific antibody; 33.1% were treated with a non-BCMA-directed bispecific antibody. Baseline characteristics, as well as prior lines of therapy and refractoriness status, were comparable between BCMA and non-BCMA groups. Median follow-up duration was 5.35 and 5.6 months in each group, respectively.

Across the whole cohort, cytokine release syndrome was reported in 59.6% of patients; 50% reported infections, 41.86% reported neutropenia, 37.32% reported anemia, and 36.41% reported lymphopenia.

Those who received non-BCMA-targeting bispecific antibodies demonstrated no significant difference in all grade and type of hematologic toxicities, including neutropenia, anemia, lymphopenia, leukopenia, and thrombocytopenia combined, vs BCMA-targeting bispecific antibodies. However, investigators noted, there was a “significant difference observant” when comparing BCMA-targeting vs non-BCMA-targeting bispecific antibodies in terms of combined grade 3/4 hematologic toxicity. Patients in the BCMA-targeting bispecific antibody group also had significantly worse hypogammaglobulinemia, while patients in the non-BCMA-targeting bispecific antibody group had a significantly higher overall cytokine release syndrome rate—although both groups experienced similar rates of grade 3/4 cytokine release syndrome.

“The use of [bispecific antibodies] in multiple myeloma has demonstrated remarkable efficacy; however, these have been linked to a unique adverse event profile,” the researchers wrote. “Our results showed that non-BCMA [bispecific antibodies] were associated with less hematotoxicity…whereas BCMA [bispecific antibodies] were associated with less cytokine release syndrome rates.”

“This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes,” they concluded.

Reference

1. Golmohammadi M, Dima D, Albayyadhi M, Moradi A, Raza S, Jaberi-Douraki M. Pooled analysis on bispecific antibody-related toxicities in multiple myeloma. Presented at: 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Abstract 1953.