Changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody therapy in patients with relapsed refractory multiple myeloma (RRMM).

8019 Background: There is a paucity of granular data on infection risk with bsAb targeting BCMA and GPRC5D in RRMM. Methods: We identified and followed 80 patients treated with bsAb therapy at 3 institutions in early-phase clinical trials between 2019 and 2022. Baseline demographic, disease and infection-specific variables were collected from the beginning of treatment to the last follow-up or 3 months after the study exit. Results: A total of 86 treatment courses were included, 56 patients received BCMA bsAb,15 GPRC5D bsAb combination with CD38MoAb + / -IMiD (GPRC5Dc), and 15 GPRC5D bsAb monotherapy (GPRC5Dm). The median age was 70 (45-91) years and 48% (n = 41) were females. Racial/ethnic minorities accounted for 27% (n = 24) of patients included. A total of 117 infections were observed, 89 in the BCMA group, 24 in the GPRC5Dc group and 4 with GPRC5Dm.The infection rate per 100 days in recipients of BCMA bsAb and GPRC5D bsAb were 0.56 and 0.40 (p = 0.34), respectively. There was a greater incidence of high-grade infections (≥ grade 3) with BCMA bsAb treatment compared to GPRC5D bsAb (p = 0.01). Grade 5 events were observed in 8% (n = 7) of patients treated with BCMA bsAb compared to none with GPRC5D bsAb. The proportion of bacterial, viral, and fungal infection in the BCMA group were 56% (n = 50), 37% (n = 37), and 7% (n = 6) respectively and that in GPRC5D group were 46% (n = 13), 43% (n = 12), 11% and (n = 3) respectively. Of the infections during BCMA bsAb therapy, 76% (n = 67) required hospitalization compared to 54% (n = 15) with GPRC5D bsAb (p = 0.02). At 18 months, the cumulative incidence of all-grade infection in the BCMA and GPRC5D group were 72% and 47%, respectively (p = 0.05). The cumulative incidence of ≥ grade 3 infection at 18 months was higher at 60% with BCMA bsAb compared to 29% with GPRC5D bsAb (p = 0.01). The cumulative mean number of recurrent infections by 18 months with BCMA bsAb was 3.2 (95% CI 2.33-4.58) and 1.4 (95% CI 0.77-2.60) with GPRC5D bsAb (p = 0.25). In multivariate analysis, the use of BCMA bsAb, GPRC5D combination therapy and prior infections with bsAb therapy was associated with a significantly higher risk of all-grade and grade≥3 infections. Conclusions: There is a significant risk of infections with bsAb therapy in RRMM with higher cumulative incidence of infection, higher grade infection and infections that require hospitalization with BCMA bsAb compared to GPRC5D bsAb. There were seven grade 5 events noted, all in patients treated with BCMA bsAb. Additionally, GPRC5D combination therapy with CD38MoAb +/- IMiDs conferred a higher risk of infections compared to GPRC5D monotherapy.