Immunoglobulin kinetics and infection patterns across venetoclax-based regimens in chronic lymphocytic leukemia

CLL causes immune dysfunction, which drives infections and is responsible for significant morbidity. We sought to build on prior literature suggesting venetoclax-based treatments may restore humoral immunity. In a retrospective single-center study of 93 patients (98 treatment courses) across venetoclax monotherapy, venetoclax plus anti-CD20 monoclonal antibody (mAb), and venetoclax plus BTK inhibitor regimens, we tracked immunoglobulin levels and infections. We found Ig patterns over time differed by regimen, with IgA suppression most statistically significant with anti-CD20 combinations. Superior IgA reconstitution (SIR) occurred in 21% of patients and was not associated with undetectable minimal residual disease (uMRD). Despite Ig recovery, cumulative infection burden did not differ by MRD status. Our findings suggest that while there is reconstitution of humoral immunity, immunoglobulin levels alone do not determine infection susceptibility.