Recent Bendamustine Treatment before Apheresis Has a Negative Impact on Outcomes in Patients with Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy

Abstract

PURPOSE Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure. METHODS The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients. RESULTS The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes. CONCLUSION Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.