Risk of Infections Higher With Bispecific Antibody Therapy for Multiple Myeloma

More vigilant screening and antimicrobial prophylaxis are suggested for patients with multiple myeloma (MM) undergoing treatment with bispecific antibodies due to a higher risk of treatment-related infections, according to study results published in Cancer Advances.

Bispecific antibodies are a novel immunotherapy. The agents work by forming immune synapses between T-cell surface marker CD3 and malignant cell markers, such as B-cell maturation antigen (BCMA). Plasma cells, as well as T-cells, are so effectively depleted by these agents that patients are at increased risk of developing infections.

Therefore, a team of researchers conducted a systematic review and meta-analysis of studies to determine the prevalence of infection in patients with MM treated with bispecific antibodies. They also sought to better characterize the infection risks.

The researchers identified 16 clinical trials representing 1666 patients. Twelve studies, with 1477 patients, examined monotherapy with bispecific antibodies. The remaining 4 trials, representing 189 patients, focused on combination therapy that included a bispecific antibody.

Primary outcome was prevalence of all-grade infection in patients with MM. Prevalence of all-grade infections was 56% (95% CI, 0.48-0.65) with high heterogeneity (I²=92%).

All-grade infections among patients treated with BCMA-bispecific monotherapy (965 patients [51%; 95% CI, 0.38-0.63]) were comparable to all-grade infections in patients treated with non-BCMA-bispecific monotherapy (501 patients [55%; 95% CI, 0.42-0.68]).

However, in studies of a bispecific in combination with another agent, all-grade infections were significantly higher compared with monotherapy (71% vs 52%), whereas grade 3 or higher infections with combination therapy were comparable to monotherapy (26% vs 24%). This effect was attributed to the BCMA-targeting agents, as only 1 study involved a non-BCMA-targeting agent. Additionally, prevalence of grade 3 or higher neutropenia was greater with BCMA-combination therapy than BCMA monotherapy (52% vs 44%).

The secondary outcomes were grade 3 or higher infections; infection-related mortality; and the proportion of bacterial, viral, and fungal infections.

Prevalence of grade 3 or higher infections was 24% (95% CI, 0.19-0.29) with high heterogeneity (I²=81%). However, incidence of grade 3 or higher infections was higher among patients treated with BCMA-targeting bispecifics (25%; 95% CI, 0.17-0.32) compared with patients treated with non-BCMA-targeting bispecific therapies (20%; 95% CI, 0.16-0.23; P <.01).

Among the 1604 patients in the 14 studies that reported infection-related mortality, 65 deaths were attributed to infection (random effects model 3%; 95% CI, 0.01-0.04).

Four observational studies, with a total of 141 patients, reported the causative pathogen for infection, and 68% of the 293 infection events were confirmed microbiologically: 49% were viral, 45% were bacterial, and 6% were fungal. Approximately half of the infection events required hospitalization.

Although the researchers acknowledge that the data are evolving, they conclude that “the high rates of viral infection and the occurrence of infections classically associated with T-cell depletion highlight the importance of antimicrobial prophylaxis in bispecific-treated patients.”

The researchers recommend frequent analysis of longer-term infection outcomes, particularly for patients with MM treated with bispecific antibodies to define duration of infection risk and assess the effect of long-term T-cell depletion.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Reynolds G, Cliff ERS, Mohyuddin GR, et al. Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis. Blood Adv. Published online July 19, 2023. doi:10.1182/bloodadvances.2023010539