Influence of B cell or plasma cell-targeted CAR-T cell therapy on humoral immunity and vaccine immunogenicity: The HICAR study

Humoral immune-related adverse events, including hypogammaglobulinemia and B cell depletion, pose long-term infection risks after chimeric antigen receptor T cell therapy (CARTx) for hematologic malignancies. This prospective study evaluated the kinetics of pathogen-specific humoral immunity prior to and up to a year after CARTx targeting CD19 and CD20 (B cells) or BCMA (plasma cells) in 100 and 28 individuals, respectively. Antibodies were tested for 12 vaccine-preventable pathogens and using comprehensive high-throughput antibody profiling. A subset of 72 participants were evaluated for post-CARTx vaccine responses. Pathogen-specific humoral immunity did not significantly change after CD19- and CD20-targeted CARTx, but these individuals lacked seroprotective antibodies for up to one-third of routine vaccine-preventable pathogens. BCMA-CARTx recipients had a modest but non-significant increase in pathogen-specific humoral immunity after CARTx but still lacked seroprotective antibodies for nearly half of tested vaccine-preventable pathogens. Pre-vaccination B cell count ≥20 cells/μL was the main predictor of vaccine response.