TOPLINE:

T-cell-engaging therapies were associated with a high burden of prolonged infections in patients with multiple myeloma, most of which were low grade. Patients receiving B-cell maturation antigen (BCMA) bispecific antibodies had more frequent and prolonged infections, whereas those receiving G protein-coupled receptor class C group 5 member D (GPRC5D)-directed bispecific antibodies had fewer events and faster recovery; symptomatic days accounted for 20% vs 9% of treatment time with BCMA bispecific antibodies vs GPRC5D bispecific antibodies.

METHODOLOGY:

• Chimeric antigen receptor (CAR) T-cell therapy and BCMA or GPRC5D-targeting bispecific antibodies are effective treatment options for multiple myeloma; however, infections, including serious and fatal complications, remain a major concern, and prolonged, low-grade infections are often underreported.
• To address this, researchers conducted a single-center retrospective study and analyzed infectious complications in 137 patients with multiple myeloma who received BCMA-directed CAR T cells (n = 58), BCMA-directed bispecific antibodies (n = 47), or GPRC5D-directed bispecific antibodies (n = 32) between October 2016 and December 2023.
• Most patients had extensive prior therapy; triple-refractory disease was seen in 91%, 83%, and 100% of the CAR T-cell, BCMA bispecific antibody, and GPRC5D bispecific antibody cohorts, respectively, and penta-refractory disease in 71%, 55%, and 81%, respectively. Polyvalent immunoglobulin G (IgG) replacement was consistently used for IgG levels < 400 mg/dL.
• Infections were graded and tracked from treatment initiation until the start of subsequent therapy, and their duration was clinically recorded on the basis of the number of days patients experienced symptoms.

TAKEAWAY:

• Overall, the incidence of infections was 76% in the CAR T-cell group, 85% in the BCMA bispecific antibodies group, and 81% in the GPRC5D bispecific antibodies group. Most infections were low grade (grade 1-2), accounting for more than 80% of events, and the most common infection sites were the upper and lower respiratory tracts.
• Severe infections (grade 3-5) occurred in 19% of the CAR T-cell recipients, 19% of the BCMA bispecific antibodies recipients, and 8% of the GPRC5D bispecific antibodies recipients. All five fatal infections in the CAR T-cell group occurred within 3 months after infusion and were associated with high-grade neutropenia.
• In multivariate analysis, BCMA bispecific antibodies (odds ratio [OR], 4.1; P = .04) were associated with a higher risk for severe infections than GPRC5D bispecific antibodies therapy. CAR T cells were also associated with an increased risk, but the association wasn’t statistically significant (OR, 3.4; P = .19). Intravenous IgG substitution reduced the risk for severe infection (OR, 0.2; P  = .001).
• BCMA bispecific antibodies were associated with more frequent and prolonged infections, whereas GPRC5D bispecific antibodies therapy was associated with fewer events and faster recovery; symptomatic days accounted for 20% vs 9% of treatment time with BCMA bispecific antibodies vs GPRC5D bispecific antibodies.

IN PRACTICE:

“A key novel finding of our study is the high burden of prolonged, low-grade infectious complications during [bispecific antibody] therapy,” which “substantially impact patients’ quality of life,” the authors of the study wrote. The findings “highlight an urgent need to investigate treatment strategies such as fixed-duration regimens or reduced maintenance dosing after deep responses to facilitate immune system recovery and improve patient outcomes.”

SOURCE:

The study, led by Julia Mersi, University Hospital of Würzburg, Würzburg, Germany, was published online as a research letter in Blood Advances.

LIMITATIONS:

The study was limited by its retrospective nature, the heterogeneity of the subgroups (including patients receiving monotherapy, combination therapy, and sequential therapies), and the small sample size, which may have limited the statistical power to detect differences in infection rates.

DISCLOSURES:

The authors did not disclose any funding source. Mersi declared serving in an advisory role for Johnson & Johnson and Pfizer and receiving honoraria from Johnson & Johnson, Sanofi, Pfizer, and SkylineDx. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.