ZUMA-2 Data Support Earlier-Line Role for Brexu-Cel in High-Risk R/R MCL Subgroups

Tom van Meerten, MD, PhD

With its demonstrated efficacy in BTK inhibitor–naive relapsed/refractory mantle cell lymphoma (MCL), brexucabtagene autoleucel (brexu-cel; Tecartus) may have a role for the treatment of patients with high-risk features earlier in the treatment course, according to Tom van Meerten, MD, PhD.

Results from cohort 3 of the phase 2 ZUMA-2 trial (NCT04880434), which evaluated brexu-cel in this patient population, were presented at the 2024 ASH Annual Meeting. At a median follow-up of 15.5 months (range, 5-15), the overall response rate (ORR) with brexu-cel was 91% (95% CI, 83%-96%). This comprised a complete response (CR) rate of 73% and a partial response rate of 17%. Moreover, high ORRs were reported among patients with confirmed TP53 mutations (n = 15/15; 100%), greater than the median tumor burden at baseline (n = 38/39; 97%), Ki-67 scores of at least 50% (n = 17/18; 94%), intermediate- or high-risk simplified MCL International Prognostic Index scores (n = 56/63; 89%), and prior bendamustine exposure (n = 19/23; 83%).

“The good news is that with this therapy, the patients with higher-risk MCL do respond, [including those with] TP53 mutations, blastoid morphology, and high Ki-67 [scores],” said van Meerten, a hematologist in the Department of Hematology at the University Medical Center Groningen, Netherlands.

In an interview with OncLive®, van Meerten briefly touched on the design and patient population of cohort 3 of the ZUMA-2 study, detailed the efficacy and manageable safety profile of brexu-cel in BTK inhibitor–naive patients, and discussed the agent’s use in clinical practice for select patient subgroups.

OncLive: What should be known about the study design and patient population enrolled in cohort 3 of ZUMA-2?

van Meerten: Cohort 3 of the ZUMA-2 study [consisted of] patients with relapsed/refractory MCL who had not been exposed to BTK inhibitors before. These patients had relapsed or refractory disease and were in need of therapy. It is in this patient cohort that brexu-cel is being studied as a potentially curative treatment option.

These patients [received] a previous line of therapy; most often, it was chemoimmunotherapy. [Additionally,] 86% of the patients had relapsed disease, and 14% of the patients were refractory to their first line of therapy.

What key efficacy and safety results from cohort 3 were reported at the 2024 ASH Annual Meeting?

The primary end point of the study is ORR, and key secondary end points are safety, progression-free survival, duration of response, and overall survival. Cohort 3 of this study met its primary end point, [with an] ORR of 91%, and [73%] of the patients obtained a CR.

There were no new safety signals, so all the adverse effects [AEs] are well known for this kind of therapy. However, grade 3 or higher safety signals [included] decreased white blood cell counts, neutropenia, decreased neutrophil [counts], and therapy-related AEs, such as cytokine release syndrome [CRS]. Regarding severity, CRS [events of] grade 3 or higher [were] only [observed] in 6% of patients. Another therapy-related AE was immune effector cell–associated neurotoxicity syndrome [ICANS]. Grade 3 or higher ICANS was [reported] in [21%] of patients.

How might these results influence the use of brexu-cel in clinical practice?

[Brexu-cel] is registered [by the European Medicines Agency] for patients who have relapsed or refractory disease after [prior receipt of] BTK inhibition. We know that BTK inhibition is a good treatment option for patients with MCL, but patients who do not respond have a poor prognosis. [Additionally], some patients have high-risk features of MCL, namely, TP53 mutations or blastoid morphology, and BTK inhibition is not that [effective for] those patients. That would be the ideal population [in which] to skip BTK inhibition and go right to the therapy that is most effective. That is brexu-cel, in this case.

Reference

van Meerten T, Kersten MJ, Iacoboni G, et al. Primary analysis of ZUMA-2 cohort 3: brexucabtagene autoleucel (brexu-cel) in patients (pts) with relapsed/refractory mantle cell lymphoma (r/r MCL) who were naive to Bruton tyrosine kinase inhibitors (BTKi). Blood. 2024;144(suppl 1):748. doi:10.1182/blood-2024-198021