Late infectious complications after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphomas (LCBL): Real-world predictors and outcomes.

Abstract

7022 Background: CD19-directed CAR-T therapy is a curative option for patients (pts) with relapsed/refractory (R/R) LBCL. Infectious complications are a major source of morbidity and non-relapse mortality (NRM). While early infections are attributed to lymphodepleting chemotherapy and management of immune-related toxicities, real-world data defining predictors of late infections after CAR-T remain limited. Methods: We performed a single-center retrospective study of adult pts with R/R LBCL, including transformed indolent lymphomas, treated with anti-CD19 CAR-T. Infectious events were defined by compatible clinical features supported by laboratory, microbiologic, or radiographic evidence. Early infections were defined as ≤30 days post-infusion and late infections as >30 days. Logistic regression assessed associations with late infection risk. Multivariable models included a priori selected clinically relevant covariates. Stepwise logistic regression was performed as a sensitivity analysis. Results: Ninety-five pts were included (median age 65 years; median follow-up 32 months). Most pts received axi-cel (88%); 10% received liso-cel and 2% tisa-cel. Salvage and/or bridging therapy prior to CAR-T was administered in 59% of pts. Early infections occurred in 16% of pts, while 63% experienced late infectious complications. Among patients with late infections, 53% were in remission post CAR-T; 43% had both viral and bacterial infections over time, 33% viral only, 22% bacterial only, and 2% fungal overall. Hypogammaglobulinemia (IgG <400 mg/dL at day +30 and/or +90) occurred in 48%, and grade 4 neutropenia between days +30 and +90 in 31%. Five-year NRM was 12%, with infections contributing to 80% of deaths. On univariate analysis, hypogammaglobulinemia was associated with higher infection risk (OR 2.38, 95% CI 1.00–5.85; p=0.053). After adjustment for prespecified covariates, the association was attenuated but directionally consistent (p=0.082) and remained the only variable retained on stepwise regression. Conclusions: Infectious complications are common following anti-CD19 CAR-T therapy for R/R LBCL and occur predominantly beyond 30 days post-infusion. Hypogammaglobulinemia showed a consistent association with infection risk across multiple modeling strategies. Ongoing prospective studies will clarify the role of immunoglobulin replacement in mitigating late infectious complications in CAR-T recipients.