ZUMA-2 is a single-arm, multicenter, open-label phase II study that investigated leukapheresed adults with mantle cell lymphoma whose disease was refractory to or had relapsed after up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy; anti-CD20 monoclonal antibody therapy; and the Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib or acalabrutinib. Cohort 3 of ZUMA-2 assessed treatment of brexucabtagene autoleucel in 86 patients who did not receive treatment with a BTK inhibitor. Results from a primary analysis of cohort 3 were reported by van Meerten et al at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition.1
At a median follow-up of 15.5 months (range, 1.4–27.1 months), the primary endpoint was met, with an objective response rate of 91% (95% confidence interval [CI] = 82.5%–95.9%; P < .0001). A complete response was reported in 73% of patients (95% CI = 62.6%–82.2%); 17% (95% CI = 10.1%–27.1%) had a partial response; 3% (95% CI = 0.7%–9.9%) had stable disease; and 3% (95% CI = 0.7%–9.9%) had progressive disease as best response to brexucabtagene autoleucel. Preliminary follow-up indicated that the median duration of all time-to-event endpoints was not yet met. The 12-month duration of response, progression-free survival, and overall survival rates were 80% (95% CI = 69.1%–87.9%), 75% (95% CI = 64.5%–83.4%), and 90% (95% = 80.7%–94.4%), respectively.
No new safety signals were detected, with a low rate of grade ≥ 3 cytokine-release syndrome occurring in five patients (6%) and an expected rate of grade ≥ 3 neurologic events (immune effector cell–associated neurotoxicity syndrome), occurring in 18 patients (21%).
“For years, we have seen strong, durable responses with brexucabtagene autoleucel from patients previously exposed to BTK inhibitor treatment,” said Tom van Meerten, MD, PhD, in a news release. Dr. van Meerten, of the University Medical Center Groningen, Netherlands, is the study’s lead investigator. “Patients with high-risk relapsed/refractory mantle cell lymphoma have poor outcomes, so it is encouraging to see positive results even in people who are BTK inhibitor treatment–naive. The high overall response rate, complete responses, and durable benefit demonstrated in ZUMA-2 cohort 3 indicate that brexucabtagene autoleucel can be used earlier in the treatment of relapsed/refractory mantle cell lymphoma,” he concluded.
Reference
1. van Meerten T, et al: 2024 ASH Annual Meeting & Exposition. Abstract 748. Presented December 9, 2024.
