Dr van Meerten on the Optimal Use of Brexu-Cel in BTK Inhibitor–Naive MCL

“We know that BTK inhibition is a good option for patients with MCL, but patients who do not respond have poor prognoses. [Additionally], some 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, a hematologist in the Department of Hematology at the University Medical Center Groningen, discusses the optimal role for brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with BTK inhibitor–naive relapsed/refractory high-risk mantle cell lymphoma (MCL).

At the 2024 ASH Annual Meeting, results from an analysis of cohort 3 of the phase 2 ZUMA-2 trial (NCT04880434) were presented by van Meerten and colleagues. This study evaluated brexu-cel—an autologous CD19-directed CAR T-cell therapy—in patients with MCL and high-risk disease features, including TP53 mutations, blastoid morphology, and elevated Ki-67 proliferation index. The therapy generated high objective response rates and induced durable remissions across all high-risk subgroups. Moreover, the median duration of response and progression-free survival outcomes indicated sustained clinical benefit with the agent in this population. The safety profile was consistent with that from previous reports, and no new safety signals were observed.

Brexu-cel is approved by the European Medicines Agency for use in patients with relapsed or refractory MCL following BTK inhibitor therapy, van Meerten reported. 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 explained. For such patients, skipping BTK inhibitors and initiating treatment with brexu-cel may provide the most effective treatment avenue, van Meerten stated. These findings support the consideration of brexu-cel as a viable frontline cellular therapy option for select patients with high-risk MCL who may not derive optimal benefit from BTK inhibition, he concluded.