A primary analysis of ZUMA-2, reported at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, demonstrated durable responses to brexucabtagene autoleucel in patients with Bruton’s tyrosine kinase (BTK) inhibitor–naive mantle cell lymphoma. The findings from cohort 3 of the study were presented by Tom van Meerten, MD, PhD, of the University Medical Center Groningen, the Netherlands, and colleagues (Abstract 748).
ZUMA-2 is a single-arm, multicenter, open-label phase II study that investigated adult patients (≥ 18 years old) with mantle cell lymphoma whose disease was refractory to or had relapsed following up to five prior lines of therapy, including anthracycline- or bendamustine-containing chemotherapy; anti-CD20 monoclonal antibody therapy; and the BTK inhibitors ibrutinib or acalabrutinib. All patients had undergone leukapheresis. Cohort 3 of ZUMA-2 assessed treatment with brexucabtagene autoleucel in 86 patients who did not receive treatment with a BTK inhibitor.
Safety and Efficacy
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 their best response to brexucabtagene autoleucel.
The investigators reported that this efficacy was durable. 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% CI = 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%).
Summary
“For years, we have seen strong, durable responses with [brexucabtagene autoleucel] from patients previously exposed to BTK [inhibitor] treatment,” said Dr. van Meerten, the study’s lead investigator, in a news release. “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.
Disclosure: Dr. van Meerten has served as a consultant for Janssen, Eli Lilly, Kite, and BMS/Celgene; has received research funding from Genentech, Kite, BMS/Celgene, and Siemens; and has received honoraria from Kite and BMS/Celgene. For full disclosures of all study authors, visit ash.confex.com.
