Dr van Meerten on the Role of Brexu-Cel in High-Risk MCL

“The good news is that with [axi-cel],patients with high-risk MCL do respond. [Patients with] TP53 mutations, blastoid morphology, and high Ki-67 have a good response to therapy. Hopefully, the data are convincing [enough to support] the FDA approval of Brexu-cel in patients with relapsed/refractory disease who have been exposed to BTK [inhibitors].”

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

The trial assessed the efficacy and safety of this autologous CD19-directed CAR T-cell therapy, in a cohort of patients with high-risk disease features, including TP53 mutations, blastoid morphology, and high Ki-67 proliferation index, van Meerten begins. These characteristics are associated with aggressive disease behavior and poor prognostic outcomes, making this a critical population for evaluation.

Results presented at the 2024 ASH Annual Meeting demonstrated that brexu-cel induced high response rates and led to durable remissions in patients with high-risk MCL . Notably, responses were seen across all high-risk subgroups. The median duration of response and progression-free survival suggested sustained clinical benefit in this population.

The safety profile of brexu-cel was consistent with previous reports in relapsed/refractory MCL, van Meerten continues. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were the most frequently observed toxicities, he adds. However, van Meerten highlights that these adverse effects were generally manageable with established mitigation strategies, including early intervention with corticosteroids and IL-6 inhibitors.

Van Meerten emphasizes that the use of brexu-cel for BTK inhibitor–naive patients with MCL represents a potential shift in the treatment paradigm for this disease. The ability of CAR T-cell therapy to elicit durable responses in this patient population underscores its therapeutic potential beyond previously treated patients. Pending further validation, these findings could support regulatory approval for brexu-cel in the relapsed/refractory setting for patients without prior BTK inhibitor exposure, van Meerten concludes.