Infectious complications following bispecific antibody or CAR T therapy in adult patients with hematologic malignancies: a retrospective database analysis

Abstract

T-cell redirection therapies, including bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T therapy, have transformed the treatment of relapsed or refractory hematologic malignancies. However, comparative data on infectious complications between these treatments remain limited. We performed a propensity score-matched analysis of adults with hematologic malignancies treated with BsAbs or CAR T using the TriNetX global research network. To mitigate confounding, we utilized 1:1 propensity score matching (caliper 0.1) to balance cohorts on demographics, malignancy type, comorbidities, and prior treatments. The primary outcome was 1-year infection hazard in BsAbs vs. CAR T. We included 2 192 matched patients (1 096/group; mean age 65.8 (11.4) years for BsAbs, 65.4 (10.2) years for CAR T). Multiple myeloma was the most common malignancy (~62%). At 1 year, infection hazard was not statistically different between cohorts (BsAbs: 57% vs. CAR T: 55.9%; HR: 1.07; 95% CI: [0.96–1.20]). Early phase infection hazard (days 1–30) was lower with BsAbs but not statistically significant (HR: 0.87; 95% CI: [0.74–1.02]). However, BsAbs therapy was associated with higher infection hazard during intermediate (days 31–180; HR: 1.27; 95% CI: [1.10–1.46]) and late phases (days 181–365; HR: 1.20; 95% CI: [1.01–1.41]). In the late phase, BsAbs carried higher hazard for fungal (HR: 2.14; 95% CI: [1.26–3.64]) and viral pathogens (HR: 1.32; 95% CI: [1.02–1.73]). Respiratory tract infections were the most frequent complication and were higher with BsAbs across all time windows (1-year: 35.4% vs. 30.4%; HR: 1.32; 95% CI: [1.14–1.53]). In conclusion, among patients captured within TriNetX, the overall observed 1-year infection rate did not differ significantly between BsAbs and CAR T therapy. However, BsAbs therapy was associated with higher coded rates of late-onset infections after extensive adjustment, although residual confounding from disease severity and treatment duration remains possible. Further studies must better define this infection burden and optimize prevention strategies.