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Background <p>Treatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after ≥ 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study (<i>N</i> = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2.</p> Methods <p>The primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 × 10<sup>6</sup> anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 × 10<sup>6</sup> anti-CD19 CAR T cells/kg (brexu-cel).</p> Results <p>Median follow-up for the pivotal cohort (<i>N</i> = 68) was 67.8 months (range, 58.2–88.6) with a median DOR of 36.5 months (<i>n</i> = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5–60.2; <i>N</i> = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response (<i>n</i> = 46). The 5-year incidence of cumulative relapse-related and non-relapse–related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel–treated patients (<i>N</i> = 10) and Cohort 2 (<i>N</i> = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient.</p> Conclusions <p>Patients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel–treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics.</p> Trial registration <p>NCT02601313 and NCT05041309.</p>

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Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2

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  • 发表日期：

    2026年4月27日

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  • Javier Muñoz,
  • Frederick L. Locke,
  • Patrick M. Reagan,
  • Andre Goy,
  • Caron A. Jacobson,
  • Brian T. Hill,
  • John M. Timmerman,
  • Ian W. Flinn,
  • David B. Miklos,
  • John M. Pagel,
  • Marie José Kersten,
  • Edouard Forcade,
  • Max S. Topp,
  • Roch Houot,
  • Amer Beitinjaneh,
  • Dan Zheng,
  • Mengru Chang,
  • Wangshu Zhang,
  • Rhine R. Shen,
  • Rita Damico Khalid,
  • Ioana Kloos,
  • Michael L. Wang

摘要

Background

Treatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after ≥ 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study (N = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2.

Methods

The primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 × 106 anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 × 106 anti-CD19 CAR T cells/kg (brexu-cel).

Results

Median follow-up for the pivotal cohort (N = 68) was 67.8 months (range, 58.2–88.6) with a median DOR of 36.5 months (n = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5–60.2; N = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response (n = 46). The 5-year incidence of cumulative relapse-related and non-relapse–related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel–treated patients (N = 10) and Cohort 2 (N = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient.

Conclusions

Patients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel–treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics.

Trial registration

NCT02601313 and NCT05041309.