Respiratory infections predominate after day 100 following B-cell maturation antigen–directed CAR T-cell therapy

Abstract

Infections are an important complication after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy and risks may differ between the early and late periods. We evaluated infections in 99 adults who received a first BCMA-directed CAR T-cell therapy (commercial and investigational autologous BCMA CAR T-cell products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded until day 365, if patients experienced symptoms with a microbiologic diagnosis, or for symptomatic site-specific infections treated with antimicrobials. One-year cumulative incidence functions were calculated based on time to first respiratory infection using dates of infection-free death and receipt of additional antineoplastic therapies as competing risks. Secondary analysis evaluated risk factors for late respiratory infections using univariate and multivariable Cox regression models. Thirty-seven patients (37%) experienced 64 infectious events over the first year after BCMA-directed CAR T-cell therapy, with 42 early infectious events (days, 0-100), and 22 late infectious events (days, 101-365). Respiratory infections were the most common site-specific infection and the relative proportion of respiratory infections increased in the late period (31% of early events vs 77% of late events). On multivariable analysis, hypogammaglobulinemia (hazard ratio [HR], 6.06; P = .044) and diagnosis of an early respiratory viral infection (HR, 2.95; P = .048) were independent risk factors for late respiratory infection. Respiratory infections predominate after BCMA CAR T-cell therapy, particularly after day 100. Hypogammaglobulinemia and diagnosis of an early respiratory infection are risk factors for late respiratory infections that may be used to guide targeted preventive strategies.

Topics & Concepts