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<p>Children with relapsed or refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) have a poor prognosis with approved therapies. Chimeric antigen receptor (CAR)-T cells are approved for adults with R/R B-NHL, but pediatric data is lacking. We report on 13 children with R/R mature B-NHL enrolled on a clinical trial for CD19 CAR-T cells harboring CD28 costimulation. Twelve patients were infused with CAR-T cells, and one had progressed and died prior to infusion. Toxicities included cytokine release syndrome in 8 patients and neurotoxicity in 6, including two patients with grade 4 neurotoxicity. All patients responded to CAR-T cells, including a complete response in 6, complete metabolic response in 2 and partial response in four. The median event-free survival was 15.2 months and median overall survival was not reached. Outcome differed by disease type, as most patients with primary mediastinal B-cell lymphoma had long term remissions, while only two of seven patients with Burkitt lymphoma were long term survivors. Thus, initial response may suffice for certain patients, but further consolidative strategies should be studied in patients with R/R Burkitt lymphoma.</p>

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CD28-costimulated CD19 CAR-T cells for pediatric mature non-Hodgkin B-cell lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月23日

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  • Alon Abramovich,
  • Etai Adam,
  • Adi Shapira,
  • Daphna Hutt,
  • Orit Itzhaki,
  • Bella Bielorai,
  • Amos Toren,
  • Elad Jacoby

摘要

Children with relapsed or refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL) have a poor prognosis with approved therapies. Chimeric antigen receptor (CAR)-T cells are approved for adults with R/R B-NHL, but pediatric data is lacking. We report on 13 children with R/R mature B-NHL enrolled on a clinical trial for CD19 CAR-T cells harboring CD28 costimulation. Twelve patients were infused with CAR-T cells, and one had progressed and died prior to infusion. Toxicities included cytokine release syndrome in 8 patients and neurotoxicity in 6, including two patients with grade 4 neurotoxicity. All patients responded to CAR-T cells, including a complete response in 6, complete metabolic response in 2 and partial response in four. The median event-free survival was 15.2 months and median overall survival was not reached. Outcome differed by disease type, as most patients with primary mediastinal B-cell lymphoma had long term remissions, while only two of seven patients with Burkitt lymphoma were long term survivors. Thus, initial response may suffice for certain patients, but further consolidative strategies should be studied in patients with R/R Burkitt lymphoma.