BACKGROUND. Little is known about pathogen-specific humoral immunity in individuals with long-term remission after treatment with chimeric antigen receptor-modified T-cells (CAR-T-cells) for B-cell lineage malignancies. METHODS. We conducted a prospective cross-sectional study of CD19-targeted or BCMA-targeted CAR-T-cell therapy recipients ≥6 months post-treatment and in remission. We measured lymphocyte subsets, immunoglobulins, pathogen-specific IgG for 12 vaccine-preventable infections, and the total number of viral and bacterial epitopes to which IgG was detected (‘epitope hits’) using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections. RESULTS. We enrolled 65 children and adults a median of 20 months after CD19- (n=54) or BCMA- (n=11) CAR-T-cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. Despite this, these individuals had seroprotection to a median of 67% (IQR, 59-73%) of tested vaccine-preventable infections. Proportions of participants with seroprotection per-pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared to CD19-CAR-T-cell recipients, BCMA-CAR-T-cell recipients were half as likely to have seroprotection to vaccine-preventable infections (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22). CONCLUSIONS. Seroprotection for vaccine-preventable infections in adult CD19-CAR-T-cell recipients was comparable to the general population, but BCMA-CAR-T-cell recipients have fewer pathogen-specific antibodies. Deficits in both groups support the need for randomized vaccine and IGRT trials to determine efficacy and risk-benefit.
Carla S. Walti, Elizabeth M. Krantz, Joyce Maalouf, Jim Boonyaratanakornkit, Jacob Keane-Candib, Laurel Joncas-Schronce, Terry Stevens-Ayers, Sayan Dasgupta, Justin J. Taylor, Alexandre V. Hirayama, Merav Bar, Rebecca A. Gardner, Andrew J. Cowan, Damian J. Green, Michael J. Boeckh, David G. Maloney, Cameron J. Turtle, Joshua A. Hill