Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL

ABSTRACT Patients with B-cell lymphomas have altered cellular components of vaccine responses due to the malignancies and therapies. The optimal timing of vaccine administration relative to chemotherapy and immunotherapy remains unknown. The SARS-CoV-2 vaccine campaign created a unique opportunity to gather insights into vaccine timing because patients were challenged with a novel antigen across multiple phases of lymphoma management. We studied retrospective and prospective cohorts of patients with lymphoma and CLL who received an mRNA-based vaccine and paired serologic response with treatment dates, clinical immune parameters, and deep immunophenotyping. Reduced serologic response was observed more frequently during active therapies but nonresponders were also identified within observation and post-treatment groups. Clinical immunologic profiling demonstrated that total IgA and IgM near the time of vaccination correlated with ability to coordinate vaccine response. In individuals treated with CART-19, high-parameter immunophenotyping demonstrated that nonresponse was associated with reduced participation in B cell clusters and clusters of T follicular helper cells required for vaccine response. Together these data suggest that predictors of vaccine responsiveness vary by disease and therapeutic group. Further studies of immune health during and after cancer therapies will allow clinicians to individualize the timing of vaccines and define immunologic vulnerabilities.