Respiratory Infections Predominate after Day 100 following B-Cell Maturation Antigen-Directed CAR T-cell Therapy.
Jessica S LittleMegha TandonJoseph S HongOmar NadeemAdam S SperlingNoopur RajeNikhil C MunshiMatthew J FrigaultSara BarmettlerSarah P HammondPublished in: Blood advances (2023)
Infections are an important complication following 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 products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded through 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 following BCMA-directed CAR T-cell therapy, with 42 early infectious events (Day 0 - 100), and 22 late infectious events (Day 101 - 365). Respiratory infections were the most common site-specific infection and increased in frequency in the late period (31% of early events versus 77% of late events). On multivariable analysis, hypogammaglobulinemia (HR 6.06; p<0.04) and diagnosis of an early respiratory viral infection (HR 2.95; p=0.04) 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 preventative strategies.