Brexucabtagene Autoleucel Shows High Efficacy in BTK Inhibitor-Naive Mantle Cell Lymphoma
Key Insights
Brexucabtagene autoleucel demonstrated a 91% objective response rate in patients with relapsed or refractory mantle cell lymphoma (search) who were BTK inhibitor-naive.
The ZUMA-2 trial's cohort 3 reported a 73% complete response rate and a 17% partial response rate with brexucabtagene autoleucel in this patient population.
At 15.5 months median follow-up, the 12-month duration of response, progression-free survival, and overall survival rates were 80%, 75%, and 90%, respectively.
Brexucabtagene autoleucel has shown promising results in patients with relapsed or refractory mantle cell lymphoma (search) (MCL) who have not previously been treated with Bruton's tyrosine kinase (BTK) inhibitors. The primary analysis of cohort 3 from the ZUMA-2 trial, presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, demonstrated high overall response rates and durable remissions in this patient population.
The ZUMA-2 trial is a single-arm, multicenter, open-label phase II study. It enrolled adult patients with MCL whose disease was refractory to or had relapsed after up to five prior lines of therapy, including anthracycline- or bendamustine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. Cohort 3 specifically assessed the efficacy of brexucabtagene autoleucel in 86 patients who were BTK inhibitor-naive.
Efficacy and Durability
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% CI = 82.5%–95.9%; P < .0001). A complete response was reported in 73% of patients (95% CI = 62.6%–82.2%), while 17% (95% CI = 10.1%–27.1%) experienced a partial response. Only 3% of patients had stable disease, and 3% had progressive disease as their best response to brexucabtagene autoleucel.
Preliminary follow-up data indicated that the median duration of all time-to-event endpoints had not yet been reached. 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, suggesting a durable benefit from the treatment.
Safety Profile
The safety profile of brexucabtagene autoleucel in this BTK inhibitor-naive cohort was consistent with previous observations. A low rate of grade ≥ 3 cytokine-release syndrome was observed in 6% of patients (five individuals). Grade ≥ 3 neurologic events, also known as immune effector cell–associated neurotoxicity syndrome, occurred in 21% of patients (18 individuals).
Clinical Implications
According to Dr. Tom van Meerten from the University Medical Center Groningen, Netherlands, the study's lead investigator, these results are encouraging, especially given the poor outcomes typically seen in patients with high-risk relapsed/refractory MCL. "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 (search)," he stated.