P-018: Prior BCMA-directed bispecific antibody or CAR T is not associated with increased risk of early infections in patients treated with bispecific antibodies.

Introduction: Bispecific antibodies are associated with a higher risk of infections, 50% in a pooled analysis of 1185 patients. Risk factors for early infections with bispecific antibodies remain undefined though hypogammaglobulinemia and neutropenia are postulated to increase risk.

Methods: We undertook a retrospective analysis of all patients who received bispecific antibodies at our center between Jan 2017 to Feb 2023. The receipt of a bispecific antibody (BisAb) regimen was considered as a treatment event (TE), if a patient received two different BisAb’s regimens over a 12-month period it would be considered as two TE. Clinical predictors of risk and infection data within the first 90 days was collected for each event.

Results: Our cohort contains 90 patients with 123 TE where 40, 48 and 35 represent regimens with BCMA, GPRC5D and FcRH5 respectively. Within these 123 TE, 77 infection episodes were recorded between days 1 and 90. No infections were recorded in 68 TE, while 41 had one infection and 14 with >=2 infections (36 total).
The most common infections recorded were - 38% had Upper respiratory tract infection, 15% blood stream, 13% pneumonia, 14% GI, and 9% had CMV viremia/infection, 8% Urinary tract infections and 3% skin infections. Recurrent infections >1 was higher with BCMA directed therapies in the first 90 days (8.4 vs 17.5%).
We divided the cohorts into no infection, 1 infection episode and greater than 1 infection episode. We observed no differences in baseline characteristics between the 3 cohorts including- HR, EMD, RISS, ECOG status, number of lines of prior therapy. On treatment parameters - ANC, ALC at D1, IgG levels, receipt of IVIG, CRS grade , tocilizumab use and treatment dose steroids were also not different between the 3 groups [0,1 and 2 infections]. Multivariate analysis showed none of the covariates including receipt of BCMA vs non BCMA BisAb, HR MM, IgG at baseline, prior CART, or prior BCMA directed therapy to be significantly associated with an increased risk of infection.

Conclusions: Our results demonstrate that early infection within 90 days is not associated with specific baseline risk factors. Importantly our analysis shows that patients who received prior immune engagers are not at an increased risk of early infections and that IgG levels, ALC and ANC were also not predictive. Other risk factors including duration of prior immune engagers should be explored to identify risk factors for recurrent infections.