Risk of Infections Associated with the Use of Bispecific Antibodies in Multiple Myeloma: A Pooled Analysis

The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pre-treated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 MM patients (number of trials, n=11) were treated with a BsAb in the studied period (71.6% of patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow up was short at 6.1 months (7.5 vs. 5.2 months for BCMA vs. non-BCMA BsAbs, respectively). Adverse events (AEs) of interest included all grade neutropenia in 38.6% (n=441/1143), all grade infections in 50% (n=542/1083), all grade cytokine release syndrome (CRS) in 59.6% (n=706/1185), grade III/IV neutropenia in 34.8% (n=372/1068), grade III/IV infections in 24.5% (n=272/1110), grade III/IV pneumonia in 10% (n=52.4/506), and grade III/IV coronavirus 2019 (COVID-19) in 11.4% (n45.4/395). Non-BCMA targeted bispecific antibodies were associated with lower grade III/IV neutropenia (25.3% vs. 39.2%, P=0.001) and lower grade III/IV infections (11.9% vs. 30%, P=0.01) when compared to BCMA-targeted bispecific antibodies. Hypogammaglobulinemia was reported in 4 studies with prevalence of 75.3% (n=256/340) with intravenous immunoglobulin used in 48% (n=123/256). Death was reported in 110 patients of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.