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] 

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 

 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.

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Tom van Meerten, MD, PhD, discusses the role of brexucabtagene autoleucel in high-risk MCL.

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 

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 

 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.

Tom van Meerten, MD, PhD, discusses the efficacy and safety of brexucabtagene autoleucel in BTK inhibitor–naive relapsed/refractory MCL.

Tom van Meerten, MD, PhD

Articles

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

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