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Introduction <p>No head-to-head clinical trials have compared CD19-directed chimeric antigen receptor (CAR) T&#xa0;cell therapies for treatment of follicular lymphoma (FL). We conducted matching-adjusted indirect comparisons (MAICs) between lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel), and tisagenlecleucel (tisa-cel), to establish their relative efficacy and safety in patients with third-line or later (3L+) relapsed or refractory (R/R) FL.</p> Methods <p>Sources included individual patient data from TRANSCEND&#xa0;FL (NCT04245839) for liso-cel, summary-level data from ZUMA-5 (NCT03105336) for axi-cel, and summary-level data from ELARA (NCT03568461) for tisa-cel. For each MAIC, TRANSCEND&#xa0;FL patients who met inclusion/exclusion criteria for the comparator study were included. MAICs adjusted for clinically relevant prognostic factors identified a priori to minimize population differences between studies.</p> Results <p>After adjustment, liso-cel had a higher complete response (CR) rate than axi-cel (response ratio [RR] 1.24, 95% confidence interval [CI] 1.07‒1.43) and tisa-cel (RR 1.36, 95%&#xa0;CI 1.11‒1.68) and a higher overall response rate (ORR) than tisa-cel (RR 1.12, 95%&#xa0;CI 1.01‒1.24). Estimates numerically favored liso-cel for progression-free survival, duration of response, overall survival, and time to next treatment, though were not statistically significant. Liso-cel demonstrated better safety than axi-cel, with significantly reduced odds ratios (ORs) of grade ≥ 3 cytokine release syndrome (CRS; OR 0.07, 95%&#xa0;CI 0.01‒0.58), tocilizumab use for CRS (OR 0.20, 95%&#xa0;CI 0.09‒0.44), any-grade neurological events (NEs; OR 0.14, 95%&#xa0;CI 0.05‒0.38), and infections (OR 0.42, 95%&#xa0;CI 0.19‒0.93). Liso-cel and tisa-cel had similar safety profiles overall, excluding any-grade NEs, which was significantly lower for liso-cel (OR 0.19, 95%&#xa0;CI 0.08‒0.45).</p> Conclusion <p>After adjustment for population differences, liso-cel demonstrated a higher CR rate and numerically favorable trends of survival compared to axi-cel and tisa-cel with improved safety compared to axi-cel, and similar safety compared to tisa-cel. These findings underscore liso-cel as a potentially preferred CAR T&#xa0;cell therapy for 3L+ R/R FL. </p> <p>Graphical Abstract available for this article.</p> Graphical Abstract <p></p>

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Indirect Treatment Comparisons of Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel and Tisagenlecleucel in Third-Line or Later Relapsed or Refractory Follicular Lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月15日

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  • Alexander P. Boardman,
  • Juan Luis Reguera Ortega,
  • Pearl Wang,
  • Merav Bar,
  • Jinender Kumar,
  • Thalia Farazi,
  • Alejandro Martín García-Sancho,
  • Koji Izutsu

摘要

Introduction

No head-to-head clinical trials have compared CD19-directed chimeric antigen receptor (CAR) T cell therapies for treatment of follicular lymphoma (FL). We conducted matching-adjusted indirect comparisons (MAICs) between lisocabtagene maraleucel (liso-cel), axicabtagene ciloleucel (axi-cel), and tisagenlecleucel (tisa-cel), to establish their relative efficacy and safety in patients with third-line or later (3L+) relapsed or refractory (R/R) FL.

Methods

Sources included individual patient data from TRANSCEND FL (NCT04245839) for liso-cel, summary-level data from ZUMA-5 (NCT03105336) for axi-cel, and summary-level data from ELARA (NCT03568461) for tisa-cel. For each MAIC, TRANSCEND FL patients who met inclusion/exclusion criteria for the comparator study were included. MAICs adjusted for clinically relevant prognostic factors identified a priori to minimize population differences between studies.

Results

After adjustment, liso-cel had a higher complete response (CR) rate than axi-cel (response ratio [RR] 1.24, 95% confidence interval [CI] 1.07‒1.43) and tisa-cel (RR 1.36, 95% CI 1.11‒1.68) and a higher overall response rate (ORR) than tisa-cel (RR 1.12, 95% CI 1.01‒1.24). Estimates numerically favored liso-cel for progression-free survival, duration of response, overall survival, and time to next treatment, though were not statistically significant. Liso-cel demonstrated better safety than axi-cel, with significantly reduced odds ratios (ORs) of grade ≥ 3 cytokine release syndrome (CRS; OR 0.07, 95% CI 0.01‒0.58), tocilizumab use for CRS (OR 0.20, 95% CI 0.09‒0.44), any-grade neurological events (NEs; OR 0.14, 95% CI 0.05‒0.38), and infections (OR 0.42, 95% CI 0.19‒0.93). Liso-cel and tisa-cel had similar safety profiles overall, excluding any-grade NEs, which was significantly lower for liso-cel (OR 0.19, 95% CI 0.08‒0.45).

Conclusion

After adjustment for population differences, liso-cel demonstrated a higher CR rate and numerically favorable trends of survival compared to axi-cel and tisa-cel with improved safety compared to axi-cel, and similar safety compared to tisa-cel. These findings underscore liso-cel as a potentially preferred CAR T cell therapy for 3L+ R/R FL.

Graphical Abstract available for this article.

Graphical Abstract