In the standard-of-care setting of patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), the efficacy and toxicity of brexucabtagene autoleucel (brexu-cel) were consistent with those reported in the phase II ZUMA-2 trial, according to a study published in the Journal of Clinical Oncology. Additional findings showed tumor-intrinsic high-risk features, and possibly recent bendamustine exposure, were associated with inferior efficacy outcomes.
“Patients need not meet restrictive criteria to benefit from [chimeric antigen receptor] (CAR) T-cell therapy for MCL,” said corresponding author Michael D. Jain, MD, PhD, of Moffitt Cancer Center in Tampa, Florida. “Post-CAR-T, greater attention is needed due to the risks of infection and non-relapse death in MCL.”
Brexu-cel is an autologous anti-CD19 CAR T-cell therapy. It was approved by the U.S. Food and Drug Administration for R/R MCL based on ZUMA-2 results that showed a best overall response rate (ORR) of 91% and a best complete response (CR) rate of 68%.
Dr. Jain and colleagues reported on the clinical outcomes of 189 patients (median age = 67, 76% male) with MCL who planned to receive CAR T-cell therapy as standard-of-care across 16 U.S. institutions between August 1, 2020, and December 31, 2021. Of these, 149 patients would not have met the ZUMA-2 eligibility criteria, with the most common reasons being prior therapies, including Bruton tyrosine kinase (BTK) inhibitor-naïve, anthracycline-/bendamustine-naïve, and five lines of prior therapy; disease status, including central nervous system (CNS) involvement; and comorbidities. However, safety and efficacy outcomes were comparable with ZUMA-2.
A total of 168 patients received brexu-cel infusion. The best ORR was 90% and the best CR rate was 82%. The median progression-free survival (PFS) after brexu-cel infusion was 16.4 months, and the six- and 12-month PFS rates were 69% and 59%, respectively. Related to safety, the non-relapse mortality rate was 9.1% at one year, primarily because of infections. In addition, 8% of patients developed grade 3 or higher cytokine release syndrome (CRS) and 32% developed neurotoxicity.
Tumor-intrinsic high-risk features that were associated with a shorter PFS after brexu-cel infusion included high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant. Intention-to-treat univariable analysis showed that patients exposed to bendamustine within 24 months before infusion had shorter PFS and overall survival.
“We provided evidence for the use of CAR T-cell therapy in subgroups not previously studied on clinical trials, such as patients with CNS involvement of their lymphoma or patients who had not previously had a BTK inhibitor,” Dr. Jain said. “We found that late infections contribute to morbidity and mortality to a greater extent in MCL compared to other lymphomas treated with CAR T-cell therapy.”
The limitations of the study were the varied peri-infusion managements, including bridging therapy and CRS and immune effector cell-associated neurotoxicity syndrome management; the lack of serial biomarker and pharmacokinetic studies of CAR T cells; and the absence of central response assessment. As the study involved only 16 academic centers, a generalization of the outcomes for all cell therapy centers cannot be made.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US Lymphoma CAR T Consortium [published online ahead of print, 2023 Feb 8]. J Clin Oncol. doi: 10.1200/JCO.22.01797.
