TOPLINE:

In patients with relapsed/refractory mantle cell lymphoma (MCL) who were naive to Bruton tyrosine kinase inhibitor (BTKi) therapy, brexucabtagene autoleucel (brexu-cel) was associated with high response rates and encouraging 12-month progression-free survival (PFS) and overall survival, but also with substantial toxicity, including cytopenias, neurologic events, and infections.

METHODOLOGY:

• Although BTKis improve outcomes in MCL, most patients eventually experience disease progression. A previous study found that brexu-cel was associated with high response rates and durable benefit in BTKi-exposed patients with heavily pretreated MCL.
• In the current single-arm, multicenter phase 2 study, researchers evaluated the efficacy and safety of brexu-cel as an earlier-line salvage option in BTKi-naive patients with relapsed/refractory MCL.
• Overall, 86 patients (median age, 64 years) received brexu-cel at a target dose of 2 × 10⁶ anti-CD19 CAR T cells/kg after undergoing lymphodepleting chemotherapy with fludarabine 30 mg/m²/d and cyclophosphamide 500 mg/m²/d on days -5, -4, and -3; the median time from leukapheresis to brexu-cel infusion was 34 days.
• The primary endpoint was objective response rate; secondary endpoints included PFS, overall survival, and adverse events. The median follow-up duration among the 86 treated patients was 15.5 months.

TAKEAWAY:

• Among all patients, the overall response rate was 91%, with a complete response rate of 73%.
• The overall response rates were high across key high-risk subgroups, including patients with TP53 mutations (100%), at least 30% Ki-67 positivity (95%), and intermediate- or high-risk simplified MCL International Prognostic Index scores (89%).
• The 12-month PFS rate was 75%, and overall survival was 90%; median PFS and OS were not reached at 24 months.
• Adverse events were common, with grade ≥ 3 events reported in most patients, largely reflecting cytopenias. Cytokine release syndrome occurred in 95% of patients (grades ≥ 3, 6%), neurologic events of grades ≥ 3 in 27%, and serious infections in 23%. Overall, seven patients died due to adverse events, four of which were considered related to lymphodepleting chemotherapy and/or brexu-cel.

IN PRACTICE:

“Brexu-cel may be a suitable salvage therapy alternative to BTKi for patients with high-risk disease features; however, the potential benefit for each patient should be considered in the context of the risk for life-threatening [adverse events],” the authors wrote.

SOURCE:

The study, led by Tom van Meerten, University Medical Center Groningen, Groningen, Netherlands, was published online in Blood, alongside an accompanying editorial.

LIMITATIONS:

The study focused on the all‑treated patient population rather than the all‑enrolled cohort, which could have introduced selection bias. Additionally, serious adverse events did occur with brexu-cel treatment, but most resolved with no new safety signals.

DISCLOSURES:

This study was funded by Kite, a Gilead Company. Meerten declared receiving honoraria from Kite and reported a consulting/advisory role with Eli Lilly and Company, as well as research funding from Bristol Myers Squibb and Siemens. Six authors disclosed employment with Kite, a Gilead company, with some also reporting stock ownership in Gilead. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.