Brexu-Cel Demonstrates Efficacy, Safety in Older Patients with R/R Mantle Cell Lymphoma

R/R Mantle cell lymphoma | Image Credit:
© Tatiana Shepeleva – stock.adobe.com

Findings from a retrospective study showed that brexucabtagene autoleucel (brexu-cel; Tecartus) could represent a potential treatment option for patients over 70 years of age with relapsed/refractory mantle cell lymphoma (MCL) who do not benefit from intensive treatment. Data were presented at the 51st Annual EBMT Meeting.1

Evaluable patients (n = 202) experienced a complete remission (CR) rate of 78%, a partial remission (PR) rate of 13%, a stable disease rate of 4.5%, and a progressive disease rate of 4.5%. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 65% (95% CI, 57%-72%) and 74% (95% CI, 67%-80%), respectively.

Safety data showed that within 30 days of infusion of brexu-cel, the cumulative incidence of any-grade cytokine release syndrome (CRS) was 83% (95% CI, 77%-88%). Grade 3/4 CRS occurred at a rate of 9% (95% CI, 4%-13%). The rate of any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was 56% (95% CI, 48%-63%).

“Year of infusion was [an] important factor for CRS, highlighting the improvements [that] have been achieved through clinical experience,” lead study author Nicole Santoro, MD, PhD, said in a presentation of the data. Santoro is a member of the Hematology Unit in the Department of Oncology and Hematology at Santo Spirito Hospital in Pescara, Italy.

Brexu-Cel Background and Study Breakdown

In July 2020, the FDA approved the brexu-cel for the treatment of adult patients with relapsed/refractory MCL.2

During her presentation, Santoro noted that in past real-world studies examining brexu-cel in patients with MCL, the median age of evaluable patients was generally below 70 years.1 In this retrospective analysis, investigators evaluated the clinical outcomes and toxicity profile of the CAR T-cell therapy in patients older than 70 years of age. Data were gathered from the EBMT Registry and included patients treated from 2020 to 2024. The 202 patients included in the analysis were from 12 different countries and were treated at 87 different EBMT centers. The median follow-up was 12.7 months (range, 6.8-23.2).

The median age at diagnosis was 69.5 years (range, 66.2-72.7), and the median age at the time of brexu-cel infusion was 74.5 years (range, 72.5-76.9). At the time of infusion, 42% of patients were over 75 years of age. The majority of patients were male (80%), and they had an ECOG performance status of 0 (43%), 1 (47%), or 2 or higher (10%). Patients received brexu-cel in 2020 (1.5%), 2021 (18%), 2022 (28%), 2023 (39%), or 2024 (13%).

Thirty-three percent of patients received 1 prior line of therapy, 19% were given 2 prior lines of therapy, and 48% received at least 3 prior lines of therapy. Sixty-five percent of patients received a prior BTK inhibitor, and 21% underwent prior autologous stem cell transplant. At the time of brexu-cel infusion, 10% of patients were in complete remission, 34% were in partial remission, 10% had stable disease, and 46% had progressive disease. Ninety-eight percent of patients underwent fludarabine plus cyclophosphamide lymphodepletion, and the median time from apheresis to infusion was 38 days (range, 33-49).

Additional Efficacy and Safety Findings

Data also demonstrated that outcomes were similar between patients 70 to 75 years of age and those over 75 years of age in terms of OS (P = .133) and PFS (P = .137).

In the overall cohort, the 1-year non-relapse mortality rate was 16% (95% CI, 10%-21%), and the 1-year incidence of relapse/progression was 20% (95% CI, 14%-26%).

Among patients who died by 100 days post-infusion (n = 34), causes of death included relapse/progression (38%), other (21%), cellular therapy–related events (18%), unknown (18%), and secondary malignancy (5.9%).

A multivariate analysis also highlighted potential factors that could influence clinical outcomes. An ECOG performance status of 2 was associated with worse OS (HR, 4.6; 95% CI, 2.16-1.78; P < .001) and PFS (HR, 3.14; 95% CI, 1.54-6.4; P = .002) outcomes compared with patients who had an ECOG performance status of 0 or 1.

No potential prognostic factors were identified for non-relapse mortality outcomes. However, an ECOG performance status of 2 was also associated with worse relapse/progression outcomes (HR, 6.65; 95% CI, 2.66-14.7; P = .001).

Notably, the year of treatment (HR, 1.4; 95% CI, 1.17-1.68; P < .001) and progressive disease at baseline (HR, 1.54; 95% CI, 1.09-2.18; P = .015) were potential prognostic factors for CRS. No factors were identified for ICANS.

Disclosures: Santoro did not report any disclosures.

References

1. Santoro N, Mooyaart JE, Novak U, et al. Outcomes of patients over 70 treated with brexucabtagene autoleucel for relapsed refractory mantle cell lymphoma: a study on behalf of CTIWP of EBMT. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS17-02.
2. FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. FDA. Updated July 27, 2020. Accessed April 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brexucabtagene-autoleucel-relapsed-or-refractory-mantle-cell-lymphoma