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

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).

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.

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.