In an analysis from the U.S. Lymphoma CAR T Consortium reported in the Journal of Clinical Oncology, Wang et al found that standard-of-care treatment with brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma since its approval in this setting has been associated with response rates comparable to those in the pivotal phase II ZUMA-2 trial—despite the fact that most of the patients receiving standard-of-care treatment would not have been eligible for ZUMA-2.
The study included 189 patients who underwent leukapheresis between August 2020 and December 2021 at 16 U.S. institutions with the intent to manufacture commercial brexucabtagene autoleucel.
Of 189 patients who underwent leukapheresis, 168 (89%) received brexucabtagene autoleucel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria, with the most common reasons including prior therapies, disease status, and comorbidities.
Among the 168 patients who received brexucabtagene autoleucel infusion, the best overall response rate was 90%, with complete response in 82% of patients and partial response in 8%. The median duration of response was 17.2 months (95% confidence interval [CI] =14.4 months to not estimable). By comparison, best overall response rate in ZUMA-2 was 91%, with complete response in 68% of patients and partial response in 23%.
At a median follow-up of 14.3 months (95% CI = 12.7–15.9) after infusion, the estimates for 6- and 12-month progression-free survival were 69% (95% CI = 61%–75%) and 59% (95% CI = 51%–66%).
In univariate analysis, progression-free survival was inferior among patients with high-risk simplified MCL International Prognostic Index (hazard ratio [HR] = 3.82, P < .001), Ki-67% ≥ 50% (HR = 3.02, P = .007), TP53 aberration (HR = 1.98, P = .008), complex karyotype (HR = 2.23, P = .005), or blastoid/pleomorphic variant (HR = 1.61, P = .036).
In intention-to-treat analysis, patients with bendamustine exposure within 6 months (HR = 1.90, 95% CI = 1.11–3.28) or 6 to 24 months before leukapheresis (HR = 1.90, 95% CI = 1.10–3.30) had inferior progression-free survival after leukapheresis vs patients with no bendamustine exposure.
Median overall survival after brexucabtagene autoleucel infusion was not reached (95% CI = 18.7 months to not estimable); 6- and 12-month rates were 86% and 75%. At 12 months, nonrelapse mortality was 9.1%, with mortality primarily due to infections.
Cytokine-release syndrome occurred in 90% of patients and was grade ≥ 3 in 8%, including grade 5 in one patient. Immune effector cell–associated neurotoxicity syndrome occurred in 61% of patients and was grade ≥ 3 in 32%. Prolonged significant anemia, thrombocytopenia, and neutropenia at day 90 occurred in 5%, 11%, and 18% of patients, respectively.
The investigators concluded, “In the standard-of-care setting, the efficacy and toxicity of brexucabtagene autoleucel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of mantle cell lymphoma, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.”
Michael D. Jain, MD, of the Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a National Cancer Institute grant. For full disclosures of the study authors, visit ascopubs.org.