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<p>CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72–93] vs. 71% [95% CI 66–77], <i>p</i> = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24–50] vs. 43% [95% CI 37–49], <i>p</i> = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50–76] vs. 50% [95% CI 44–57], <i>p</i> = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, <i>p</i> = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30–52] vs. 55% [95% CI 49–60], <i>p</i> = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.</p>

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Treatment failure patterns in early versus late introduction of CAR T-cell therapy in large B-cell lymphoma

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • Magdalena Corona,
  • Andrew Ip,
  • Samantha Brown,
  • Alejandro Luna,
  • Hazim Khatib,
  • Jessica R. Flynn,
  • Sean M. Devlin,
  • Ivan Landego,
  • Giulio Cassanello,
  • Kai Rejeski,
  • Tsila Zuckerman,
  • Parastoo B. Dahi,
  • Michael Scordo,
  • Richard J. Lin,
  • Maciej Kabat,
  • Efrat Luttwak,
  • Emma Pavkovic,
  • M. Lia Palomba,
  • Jae Park,
  • Gilles Salles,
  • Heiko Schoder,
  • Doris Leithner,
  • Lori A. Leslie,
  • Miguel-Angel Perales,
  • Ofrat Beyar-Katz,
  • Gunjan L. Shah,
  • Roni Shouval

摘要

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72–93] vs. 71% [95% CI 66–77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24–50] vs. 43% [95% CI 37–49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50–76] vs. 50% [95% CI 44–57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30–52] vs. 55% [95% CI 49–60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.