Humoral vaccine responses following Chimeric Antigen Receptor T-cell therapy for hematological malignancies
Sigrun Einarsdottir, Stephanie Lobaugh, Danny Luan, Marina Gómez-Llobell, P Subramanian, Sean M. Devlin, David J. Chung, Parastoo B. Dahi, Lorenzo Falchi, Sergio Giralt, Heather Landau, Alexander M. Lesokhin, Richard J. Lin, Jennifer Kimberly Lue, Sham Mailankody, M. Lia Palomba, Jae H. Park, Gilles Salles, Michael Scordo, Silvia Escribano-Serrat, Jaime Sanz, Kai Rejeski, Roni Shouval, Saad Z. Usmani, Miguel‐Angel Perales, Gunjan L. Shah, Zainab Shahid
Abstract
This single-center, retrospective study analyzed vaccine responses in patients who received post-Chimeric Antigen Receptor (CAR) T-cell therapy vaccination between 2018 and 2024. Vaccinations were administered according to EBMT/CIBMTR recommendations and pathogen-specific IgG responses to 12 vaccine-preventable infections were assessed. Seroprotection was defined by established cut-offs or a significant fold increase in titers. A total of 73 patients that had not received intravenous immunoglobulins within the eight weeks prior to pre- or post titer were included. The median time to vaccination initiation was 13 months (range 6-66) post-CAR T. Pre and post-vaccination titers were available for 49 patients. Pre-vaccination seroprotection was high (> 85%) for tetanus and poliovirus. Among patients not seroprotected prior to vaccination, vaccine response rates were high for tetanus and polio (100%), moderate for diphtheria (75%) and haemophilus influenzae type b (62%), and lower for pertussis (48%), hepatitis A (43%), hepatitis B (44%), and pneumococcal disease (33%). CD19 CAR T recipients had higher pre-vaccination seroprotection rates than BCMA recipients, but vaccine responses did not differ significantly between groups. Pre-vaccination IgA levels were significantly associated with vaccine response, and absolute B-cell counts trended higher among responders (p = 0.054). Our findings highlight the importance of immune reconstitution in vaccine responses post-CAR T.