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Efficacy and safety of CAR T-cell reinfusion in children and young adults with R/R B-ALL

May 3, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in acute lymphocytic leukemia.

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CD19-targeted chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant responses in patients with relapsed or refractory B-cell acute lymphocytic leukemia (B-ALL). However, nearly 25–50% of pediatric patients experience relapse. One potential approach that could prevent and treat relapse after initial CAR T-cell infusion is reinfusion with the same CAR T-cell therapy.1

Here, we summarize a retrospective study published by Myers et al.1 in Blood Advances evaluating the efficacy and safety of CAR T-cell reinfusion for the prevention and treatment of relapse in children and young adults with B-ALL.

Study design1

  • This retrospective study included children and young adults with relapsed or refractory B-ALL from three clinical trials, who had received at least one reinfusion of anti-CD19 CAR T cells (CTL019 or huCART19).
  • The primary endpoint was complete response (CR) rate at Day 28 after CAR T-cell reinfusion.
  • Secondary endpoints included factors associated with a CR, cumulative incidence of relapse, overall survival, and incidence of cytokine release syndrome and neurotoxicity.

Key findings1

  • A total of 81 patients were included in the analysis.
  • Overall, 63 patients received CAR T-cell reinfusion for relapse prevention due to peripheral B-cell recovery (n = 40) and the emergence of CD19+ hematogones (n = 23).
  • 18 patients received reinfusion for relapse due to CD19+ measurable residual disease/relapse (n = 10) and non-response to initial CAR T-cell reinfusion (n = 8).

CR and survival

  • The CR rate for patients reinfused for relapse prevention was 52%.
    • Among patients with peripheral B-cell recovery, the CR rate was higher for those receiving lymphodepletion prior to CAR T-cell reinfusion vs those who did not (50% and 8%, respectively; p = 0.031).
    • Among patients with emergence of CD19+ hematogones, the CR rate was higher in patients with hematogones at ≥6 months vs 3 months vs Day 28 after initial CAR T-cell reinfusion (100%, 87%, and 0%, respectively; p = 0.009).
  • The CR rates for patients reinfused for relapse prevention/treatment are reported in Figure 1.
  • At a median follow-up of 38 months, the 24-month cumulative incidence of relapse for patients with CR vs no response was 29% vs 61%, respectively.
  • The 24-month overall survival was similar between patients with CR vs no response (90% in each).

Figure 1. CR rates after CD19 CAR T-cell reinfusion* 

BCR, B-cell recovery; CAR, chimeric antigen receptor; CR, complete response; MRD, measurable residual disease.
*Data from Myers, et al.1

Cytokine release syndrome and neurotoxicity

The incidence of cytokine release syndrome and neurotoxicity across all groups are reported in Figure 2A and 2B.

Figure 2. Incidence of A CRS and B neurotoxicity by grade 

CRS, cytokine release syndrome; CARTi, initial chimeric antigen receptor T-cell infusion; MRD, measurable residual disease.
*Data from Myers, et al.1


Key learnings
  • Reinfusion of CTL019/huCART19 has shown to extend persistence in patients reinfused for relapse prevention, thus it could help reduce relapse risk.
  • Reinfusion can also reinduce remissions in patients with CD19+ relapse.
  • Reinfusion was well tolerated, with Grade ≥3 cytokine release syndrome or neurotoxicity only observed in the measurable residual disease/relapse group.

  1. Myers RM, Devine KJ, Li Y, et al. Reinfusion of CD19 CAR T Cells for relapse prevention and treatment in children with acute lymphoblastic leukemia. Blood Adv. 2024. Online ahead of print. DOI: 1182/bloodadvances.2024012885


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