Impact of Prior Bendamustine Exposure on Chimeric Antigen Receptor T-Cell Therapy Outcomes in Follicular Lymphoma.

Prior bendamustine exposure impairs T-cell fitness and has been associated with inferior CAR T-cell therapy outcomes in large B-cell lymphoma, but follicular lymphoma (FL)-specific data are lacking. Using the TriNetX Research Network (107 healthcare organizations), we conducted a retrospective cohort study of adult patients with relapsed/refractory FL who received CD19-directed CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel). Propensity score-matched comparisons evaluated overall survival (OS) stratified by bendamustine exposure timing. Any prior bendamustine exposure was associated with inferior 2-yr OS compared with bendamustine-naive patients (58.99% versus 76.73%; HR 1.855, 95% CI 1.003 to 3.432, P = .046, n = 89). Critically, bendamustine exposure within 1 yr of CAR T-cell infusion was associated with significantly worse 2-yr OS compared with exposure more than 1 yr prior (40% versus 68%; HR 2.277, 95% CI 1.117 to 4.644; P = .020, n = 46). In contrast, patients with bendamustine exposure more than 1 yr before CAR T-cell had the same OS as bendamustine-naive patients (71% versus 72%; HR 1.045; P = .914). A dose-response analysis demonstrated a consistent, statistically significant increase in mortality risk as bendamustine exposure approached the time of CAR T-cell infusion across all 3 measures of association (P < .05). Inpatient admission within 30, 60, and 90 days of CAR T-cell was significantly higher in patients with recent bendamustine exposure. These findings are hypothesis-generating and suggest a clinically actionable 12-mo washout interval and support preferential use of nonbendamustine-containing regimens over bendamustine-based regimens in patients with FL who may require future CAR T-cell therapy.