Understanding Adverse Events With BCMA-, Non-BCMA-Targeting Bispecific Antibodies in Multiple Myeloma
Understanding the adverse event profile of bispecific antibodies can aid treatment selection and improve patient outcomes.
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.
