There is a paucity of granular data on infection risk with BCMA and GPRC5D bispecific antibodies (bsAb) in RRMM. The aim of our multi-institutional study was to characterize the incidence, etiologies, and risk-factors of infections from the start of therapy to the last follow-up or 90 days after study exit. A total of 66 patients received BCMA bsAb monotherapy, 15 GPRC5D bsAb monotherapy (GPRC5D-mono), and 15 GPRC5D bsAb combination therapy with daratumumab and/or pomalidomide (GPRC5D-combination). While the infection rate per 100 days was 0.57 for BCMA bsAb, it was 0.62 for GPRC5D bsAb-combination and 0.13 for GPRC5D bsAb-monotherapy; p=0.05. The proportion of infections that were ≥ grade 3 was higher in the BCMA bsAb group compared to the GPRC5D groups (58% vs 36% ; p=0.04). Grade 5 events were observed in 8% (n=8) of the patients, all treated with BCMA bsAb. The 9-month cumulative incidence of any grade of infection was similar in the BCMA and GPRC5D-combination groups (57% and 62%) and significantly higher than in the GPRC5D-mono group (16%), p=0.012. The cumulative incidence of ≥ grade 3 infections was highest in the BCMA group reaching 54% at 18 months, p = 0.06, Multivariate analysis showed that BCMA bsAb therapy or GPRC5D-combination therapy, history of previous infections, baseline lymphopenia, and baseline hypogammaglobulinemia were significantly associated with a higher risk of grade ≥3 infections. Our results indicate that BCMA bsAb and GPRC5D BsAb-combination therapies in RRMM are associated with higher cumulative incidence of infection and ≥ grade 3 infection compared to GPRC5D bsAb-mono.
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