Stosh Ozog, Elizabeth M. Krantz, Karyn Tindbaek, Julian Munoz, Winnie Liu, Clementine Chalal, Sara Pernikoff, Khaleel Yahya, Terry Stevens-Ayers, Sayan Dasgupta, Andrew J. Cowan, Damian J. Green, Jordan Gauthier, Brian G. Till, Rebecca A. Gardner, Mazyar Shadman, Marie Bleakley, Michael Boeckh, Jim Boonyaratanakornkit, Cameron J. Turtle, Joshua A. Hill
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 evaluates 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 are tested for 12 vaccine-preventable pathogens and using comprehensive high-throughput antibody profiling. A subset of 72 participants are evaluated for post-CARTx vaccine responses. Here, we show pathogen-specific humoral immunity does not significantly change after CD19-, CD20-, or BCMA-targeted CAR-T cell therapy (CARTx). However, seroprotective antibodies are absent for up to one-third of routine vaccine-preventable pathogens in CD19- and CD20-CARTx recipients and for nearly half of vaccine-preventable pathogens in BCMA-CARTx recipients by one-year post-CARTx. Pre-vaccination B cell count is the main predictor of vaccine response. A range of humoral related adverse events can occur after treatment of haematological malignancy with chimeric antigen receptor cell therapies. Here the authors characterise the persistence of humoral immunity and response to vaccination after patients receive B cell targeted chimeric antigen receptor T cell therapy.