In an analysis presented at the 2022 ASCO Annual Meeting (Abstract 7518) and simultaneously reported in the Journal of Clinical Oncology, Michael Wang, MD, and colleagues provided data from the 3-year follow-up of the pivotal ZUMA-2 trial of the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel in patients with relapsed or refractory mantle cell lymphoma.
Michael Wang, MD
Study Details
In the trial, 74 patients with a range of one to five prior therapies, including a BTK inhibitor, were enrolled and leukapheresed. Brexucabtagene autoleucel was successfully manufactured for 71, and 68 received a single infusion of 2 x 106 CAR T cells/kg.
Key Findings
During a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91% (95% confidence interval [CI] = 81.8%–96.7%) with complete response in 68% (95% CI = 55.2%–78.5%). Median duration of response was 28.2 months (95% CI = 13.5–47.1 months). A total of 25 patients converted to complete response after initial partial response or stable disease. At data cutoff, responses (all complete responses) were ongoing in 37% of treated patients.
Median progression-free survival was 25.8 months (95% CI = 9.6–47.6 months) and median overall survival was 46.6 months (95% CI = 24.9 months–not estimable).
Post hoc analyses indicated that objective response rates and ongoing response rates were consistent among prespecified subgroups by prior BTK inhibitor exposure or high-risk characteristics. For example, responses were ongoing at data cutoff in 41% of patients with prior ibrutinib exposure and in 44% with prior acalabrutinib exposure; in 33% to 44% of patients with Ki-67 proliferation index values of < 30% to ≥ 50%; and in 27% of those with disease progression < 24 months after initial diagnosis.
A total of 37 patients received prior bendamustine and 31 did not. Objective response was observed in 84% vs 100% and responses persisted at data cutoff in 29% vs 48%. An exploratory analysis showed that patients who received bendamustine within 6 months of apheresis had lower peak CAR T-cell levels after infusion than those with bendamustine treatment at > 6 months prior to apheresis or patients who did not receive bendamustine.
Late-onset toxicities were uncommon, with only 3% of treatment-emergent adverse events of interest occurring during long-term follow-up.
The investigators concluded, “These data, representing the longest follow-up of CAR T-cell therapy in patients with mantle cell lymphoma to date, suggest that brexucabtagene autoleucel induced durable long-term responses with manageable safety in patients with relapsed/refractory mantle cell lymphoma and may also benefit those with high-risk characteristics.”
Dr. Wang, of the Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Kite, a Gilead Company. For full disclosures of the study authors, visit ascopubs.org.
