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<p>Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are standard-of-care second-line therapies for relapsed or refractory large B-cell lymphomas, yet clinical and immunological predictors of durable benefit remain poorly defined. Here, we retrospectively analyze 64 patients treated with second-line commercial axi-cel (<i>n</i> = 35) or liso-cel (<i>n</i> = 29). Overall (66%) and complete (55%) response rates are similar between CART products. The 24-month progression-free survival (PFS) and overall survival rates are 46% and 76%, respectively. Primary refractory disease and progressive disease at infusion are associated with inferior response rates on multivariate analysis. Importantly, toxicity rate is relatively low, with 3% of patients experiencing Grade 3-4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Furthermore, lower CD4<sup>+</sup> T-cell counts at apheresis correlate with inferior PFS. Immunophenotyping reveals that higher naïve CD4<sup>+</sup> T-cell counts at apheresis predict durable response in axi-cel-treated patients. Greater CART expansion, enrichment for naïve CD8<sup>+</sup> CAR<sup>+</sup> T-cells, and lower PD1 expression at day 7 post-infusion are associated with response. Thus, these findings highlight the efficacy of second-line CART and identify disease and immune-related predictors of long-term response.</p>

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Naïve CD4+ T-cells and disease status at CART infusion correlate with clinical outcomes in real-world large B-cell lymphoma patients receiving second-line CAR T therapy

  • 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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  • Michael Schneider,
  • Luca Paruzzo,
  • Federico Stella,
  • Julia Han Noll,
  • Matthew Ho,
  • Victor Babatunde,
  • Bianca Ho,
  • Pooja Devi,
  • Elise A. Chong,
  • Stefan K. Barta,
  • Sunita D. Nasta,
  • Jakub Svoboda,
  • Jordan Carter,
  • Michael R. Cook,
  • Nasheed M. Hossain,
  • Colin J. Thomas,
  • Vrutti Patel,
  • Vitor B. de Souza,
  • Mohannad H. Alkhatib,
  • Ziyu Li,
  • Melody Tan,
  • Peter Michener,
  • Puneeth Guruprasad,
  • Antonio Imparato,
  • Alberto Carturan,
  • Patrizia Porazzi,
  • Joseph A. Fraietta,
  • Stephen J. Schuster,
  • Ivan Maillard,
  • Marco Ruella,
  • Daniel J. Landsburg

摘要

Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are standard-of-care second-line therapies for relapsed or refractory large B-cell lymphomas, yet clinical and immunological predictors of durable benefit remain poorly defined. Here, we retrospectively analyze 64 patients treated with second-line commercial axi-cel (n = 35) or liso-cel (n = 29). Overall (66%) and complete (55%) response rates are similar between CART products. The 24-month progression-free survival (PFS) and overall survival rates are 46% and 76%, respectively. Primary refractory disease and progressive disease at infusion are associated with inferior response rates on multivariate analysis. Importantly, toxicity rate is relatively low, with 3% of patients experiencing Grade 3-4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Furthermore, lower CD4+ T-cell counts at apheresis correlate with inferior PFS. Immunophenotyping reveals that higher naïve CD4+ T-cell counts at apheresis predict durable response in axi-cel-treated patients. Greater CART expansion, enrichment for naïve CD8+ CAR+ T-cells, and lower PD1 expression at day 7 post-infusion are associated with response. Thus, these findings highlight the efficacy of second-line CART and identify disease and immune-related predictors of long-term response.