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Real-world eligibility, utilization, and barriers to CAR T-cell therapy in relapsed/refractory mantle cell lymphoma

Bone Marrow Transplantation (2025)Cite this article

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Prior to the advent of chimeric antigen receptor (CAR) T-cell therapy, patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) had poor outcomes, with median overall survival (OS) of only 3–11 months after discontinuing a Bruton’s tyrosine kinase inhibitor (BTKi) [1, 2]. In the phase II ZUMA-2 trial, the CD19-directed CAR T-cell product brexucabtagene autoleucel (brexu-cel) achieved an overall response rate (ORR) of 91%, complete response (CR) rate of 68%, median progression-free survival (PFS) of 26 months, and median OS of 47 months among 68 treated patients [3]. Despite these impressive results, brexu-cel may not be accessible or suitable for all patients due to geographic, logistical, and clinical barriers, including risks of manufacturing failure, rapid disease progression precluding infusion, and potentially severe treatment-related toxicities [3,4,5,6]. While previous studies have reported outcomes of CAR T-cell therapy exclusively among approved, leukapheresed, or infused patients [3,4,5, 7, 8], data are scarce regarding real-world eligibility, utilization, and outcomes of CAR T-cell therapy across the full population of patients with R/R MCL following BTKi failure.

This retrospective, population-based study included consecutive patients aged ≥18 years with BTKi-exposed R/R MCL who initiated third-line or later treatment (henceforth referred to as the index therapy) between November 2022 and June 2025 in Alberta, Canada. During this period, brexu-cel was reimbursed via provincial health insurance for all patients with R/R MCL after ≥2 prior lines of systemic therapy including a BTKi. CAR T-cell therapy was delivered at the province’s two tertiary cancer centres in Calgary and Edmonton. The primary objective of this study was to determine the proportion of patients who were intended for and ultimately received CAR T-cell therapy. Secondary objectives included identifying barriers to treatment, describing management of ineligible patients, and assessing clinical outcomes. PFS and OS were estimated via the Kaplan-Meier method using Stata BE 17.0 (StataCorp LLC, College Station, Texas, United States). This study was approved by the Health Research Ethics Board of Alberta and performed in accordance with the relevant guidelines and regulations. Informed consent was not required for this retrospective study as it posed minimal risk to participants.

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Fig. 1: Survival Outcomes.

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Data may be available from the authors upon reasonable request.

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Authors and Affiliations

  1. Arthur Child Comprehensive Cancer Centre and University of Calgary, Calgary, Canada

    Robert Puckrin, Carolyn Owen & Mona Shafey

  2. Cross Cancer Institute and University of Alberta, Edmonton, Canada

    Vladimir Sapon-Cousineau & Anthea Peters

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  1. Robert Puckrin
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  2. Vladimir Sapon-Cousineau
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  3. Anthea Peters
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  4. Carolyn Owen
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  5. Mona Shafey
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Contributions

RP conceived the study, collected and analyzed data, and wrote the manuscript. VSC, AP, CO, and MS contributed to data analysis and revised the manuscript.

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Correspondence to Robert Puckrin.

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Competing interests

This study did not receive funding from any source. RP has received honoraria from Abbvie, Astrazeneca, Beigene, Eli Lilly, Incyte, Kite, Janssen, Pfizer, Roche, and Seagen. VSC has received honoraria from Kite. AP has received honoraria from Abbvie, Astrazeneca, Beigene, Eli Lilly, Incyte, Kite, Janssen, Roche, and Seagen. MS has received honoraria from Abbvie, AstraZeneca, Beigene, Eli Lilly, Incyte, Kite, Janssen, and Roche.

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Puckrin, R., Sapon-Cousineau, V., Peters, A. et al. Real-world eligibility, utilization, and barriers to CAR T-cell therapy in relapsed/refractory mantle cell lymphoma. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02786-w

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