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<p>Tisagenlecleucel (tisa-cel), an autologous anti-CD19 CAR T-cell therapy, has significantly improved outcomes in pediatric, adolescents and young adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). However, 30–50% experience early failure or relapse. We retrospectively analyzed 52 cases of early failures (<i>n</i> = 13) or relapses (<i>n</i> = 39), evaluating post-tisa-cel outcomes and prognostic factors. CD19 antigen loss was the only factor associated with a lower complete remission rate after salvage therapy (OR = 0.16, 95%CI [0.03–0.90], <i>p</i> = 0.04). Median overall survival (OS) was 14.5 months, with a 2-year OS of 37.4% (95%CI [24.4–50.4]), similar between early failure (38.5%) and relapse (37.0%) groups (<i>p</i> = 0.78). Patients with measurable residual disease only at salvage initiation had significantly improved 2-year OS (61.9%, (95%CI [38.1–78.8])) compared to those with overt disease (20.7%, (95%CI [8.4–36.7], <i>p</i> = 0.008)). Factors associated with inferior OS included high pre-infusion tumor burden (HR = 3.57, <i>p</i> &lt; 0.01), and prior inotuzumab ozogamicin exposure (HR = 3.81, <i>p</i> &lt; 0.01). Although salvage therapies and hematopoietic stem cell transplantation benefit some patients, 5 of 18 transplanted patients died from treatment-related toxicity, underscoring the significant associated risks. These findings highlight the poor prognosis of tisa-cel failures and the urgent need for novel strategies.</p>

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Characteristics and outcome determinants in children, adolescents and young adults who failed tisagenlecleucel for B-cell acute lymphoblastic leukemia

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Nicolas Lecornec,
  • Florence Rabian,
  • Marie-Emilie Dourthe,
  • Florian Chevillon,
  • Karima Yakouben,
  • Delphine Chaillou,
  • Sophie Caillat-Zucman,
  • Alexis Cuffel,
  • Emmanuelle Lesprit,
  • Anne Arnould,
  • Jérôme Naudin,
  • Julie Roupret-Serzec,
  • Nathalie Parquet,
  • Anne Brignier,
  • Valérie Guérin-El Khourouj,
  • Elodie Lainey,
  • Aurélie Caye-Eude,
  • Chloé Arfeuille,
  • Emmanuelle Clappier,
  • Rathana Kim,
  • Stéphanie Mathis,
  • Marie-Laure Chaix,
  • Elie Azoulay,
  • Jean-Hugues Dalle,
  • Isabelle Madelaine,
  • Jérôme Larghero,
  • André Baruchel,
  • Nicolas Boissel

摘要

Tisagenlecleucel (tisa-cel), an autologous anti-CD19 CAR T-cell therapy, has significantly improved outcomes in pediatric, adolescents and young adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). However, 30–50% experience early failure or relapse. We retrospectively analyzed 52 cases of early failures (n = 13) or relapses (n = 39), evaluating post-tisa-cel outcomes and prognostic factors. CD19 antigen loss was the only factor associated with a lower complete remission rate after salvage therapy (OR = 0.16, 95%CI [0.03–0.90], p = 0.04). Median overall survival (OS) was 14.5 months, with a 2-year OS of 37.4% (95%CI [24.4–50.4]), similar between early failure (38.5%) and relapse (37.0%) groups (p = 0.78). Patients with measurable residual disease only at salvage initiation had significantly improved 2-year OS (61.9%, (95%CI [38.1–78.8])) compared to those with overt disease (20.7%, (95%CI [8.4–36.7], p = 0.008)). Factors associated with inferior OS included high pre-infusion tumor burden (HR = 3.57, p < 0.01), and prior inotuzumab ozogamicin exposure (HR = 3.81, p < 0.01). Although salvage therapies and hematopoietic stem cell transplantation benefit some patients, 5 of 18 transplanted patients died from treatment-related toxicity, underscoring the significant associated risks. These findings highlight the poor prognosis of tisa-cel failures and the urgent need for novel strategies.