Real-world treatment patterns of patients with large B-cell lymphoma over time and into a post–CAR T approval era

ABSTRACT: A significant proportion of patients with large B-cell lymphoma (LBCL) experience relapsed or refractory (R/R) disease after first-line (1L) therapy. Chimeric antigen receptor T-cell (CAR T) therapy is approved for R/R LBCL, yet real-world use remains unclear. This retrospective study evaluated treatment patterns and survival outcomes in patients potentially eligible for CAR T in the Flatiron Health Research Database. Patients diagnosed with LBCL from 2011 to 2024 who initiated 1L therapy were assessed. Predictors of mortality before the opportunity to initiate second-line (2L) therapy were evaluated using competing risk regression models. Treatment patterns among subgroups that initiated 2L and third-line (3L) therapy based timing of US Food and Drug Administration indication approvals for CAR T were evaluated and stratified by CAR T fitness using age and Eastern Cooperative Oncology Group performance status (ECOG PS) score. Among 10 016 patients who initiated 1L therapy, 13% died within 1 year without initiating 2L therapy, and 30% initiated 2L therapy. In competing risk analyses, 11% of patients with an ECOG PS score of 0/1/unknown (combined) died within 12 months of initiating 1L therapy before being able to receive 2L therapy. Among patients deemed eligible and fit for CAR T therapy, 25% received 2L CAR T therapy, and 36% received 3L CAR T therapy. Despite its curative potential, CAR T uptake remains low in potentially eligible patients, with many dying within 1 year of initiating 1L therapy and before the opportunity to receive CAR Ts. Early collaboration between the community oncologist and CAR T center, improved access, and expanded patient awareness strategies are needed to improve CAR T therapy uptake.