Dr van Meerten on the Efficacy and Safety of Brexu-Cel in BTK Inhibitor–Naive R/R MCL

“We know that BTK inhibition is a good option for patients with MCL, but patients who do not respond have poor prognosis. [Additionally], some of the patients have high-risk features of MCL…and BTK inhibition is not that [effective for] these patients. That would be the ideal population [in which] to skip BTK inhibition and go right to [brexu-cel].”

Tom van Meerten, MD, PhD, hematologist, Department of Hematology, University Medical Center Groningen, Netherlands, discusses results from cohort 3 of the phase 2 ZUMA-2 trial (NCT04880434), which evaluated brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with BTK inhibitor–naive relapsed/refractory mantle cell lymphoma (MCL).

This study achieved its primary end point, van Meeren begins. At a median follow-up of 15.5 months (range, 5-15), the ORR with brexu-cel (n = 86) was 91% (95% CI, 83%-96%), including a CR rate of 73% and a partial response rate of 17%. High ORRs were observed in subgroups with confirmed TP53 mutations (100%; n = 15/15), tumor burdens greater than or equal to the median at baseline (97%; n = 38/39), Ki-67 scores of 50% or greater (94%; n = 17/18), intermediate- or high-risk simplified MCL International Prognostic Index (sMIPI) scores (89%; n = 56/63), and prior bendamustine exposure (83%; n = 19/23).

No new safety signals were identified, and adverse effects (AEs) were consistent with previous reports, van Meerten continues. Grade 3 or higher AEs included decreased white blood cell counts, neutropenia, and decreased neutrophil counts, he details. Cytokine release syndrome occurred in 6% of patients at grade 3 or higher, van Meerten notes. Grade 3 or higher immune effector cell–associated neurotoxicity syndrome was reported in 21% of patients, he reports.

Brexu-cel is available for patients with relapsed or refractory mantle cell lymphoma (MCL) following prior treatment with BTK inhibitors, van Meerten states. Although BTK inhibitors are effective for many patients with MCL, those with high-risk features, such as TP53 mutations or blastoid morphology, often experience poor outcomes with BTK inhibition, he says. For such patients, skipping BTK inhibitors and initiating treatment with brexu-cel may provide the most effective therapeutic option, van Meerten concludes.