Xu, Hairong

Abstract Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T-cell therapy approved for relapsed/refractory mantle cell lymphoma (R/R MCL). Here, we report real-world effectiveness and safety outcomes of brexu-cel in a prospective study of patients with R/R MCL, including subgroups based on prior treatment with Bruton's tyrosine kinase inhibitor, bendamustine, or autologous hematopoietic cell transplant (auto-HCT) and number of prior therapy lines, using Center for International Blood and Marrow Transplant Research registry data. A total of 476 patients with R/R MCL who received brexu-cel between July 2020 and December 2022 were included in the analysis. With a median follow-up of 13.5 months, the overall response rate was 91% and complete response rate was 82%. One-year overall survival and progression-free survival rates were 76% and 63%, respectively. One-year cumulative incidence of nonrelapse mortality was 8%. Prior auto-HCT was associated with better duration of response within 6 months after infusion (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.28-0.85) but greater risk of immune effector cell–associated neurotoxicity syndrome (odds ratio [OR], 1.66; 95% CI, 1.06-2.60). Prior bendamustine was associated with increased risk of prolonged thrombocytopenia (OR, 1.90; 95% CI, 1.13-3.21). In patients with 1 to 2 prior therapy lines, relapse or progression was less frequent compared with those with ≥3 prior lines (HR, 0.64; 95% CI, 0.42-1.00). Collectively, our results suggest that real-world outcomes with brexu-cel were consistent with those of the ZUMA-2 trial, regardless of prior therapy type or number of prior therapy lines.

Abstract Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell–associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.