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Safety and efficacy of allo-HSCT for patients with R/R T-ALL/LBL who achieved CR after CD7-directed CAR T-cell therapy

By Quintina Dawson

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Jun 20, 2024

Learning objective: After reading this article, learners will be able to cite a new clinical development in ALL.


CD7-directed chimeric antigen receptor (CAR) T-cell therapy has demonstrated high complete remission (CR) rates in patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL). The impact of CD7-directed CAR T-cells on transplantation outcomes in this patient population is currently unknown.1

Here, we summarize a retrospective study published by Cao et al.1 in British Journal of Haematology on the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with R/R T-ALL/LBL who achieved a CR after CD7-directed CAR T-cell therapy.1

Study design1

  • This study included patients with R/R T-ALL/LBL who underwent allo-HSCT after achieving a CR with naturally selected CD7 CAR T-cell therapy. 
  • Post transplantation outcomes were compared between patients who achieved a CR after CD7-CAR T-cell therapy vs chemotherapy alone. 
  • The primary endpoint was overall survival (OS) and leukemia-free survival (LFS).
  • Secondary endpoints included non-relapse mortality (NRM), relapse incidence, cumulative incidence of acute graft-versus-host disease (GvHD), chronic GvHD, and infections.

Key findings1

Outcomes after autologous CD7 CAR T-cell therapy

  • A total of 34 patients who achieved CR after CD7-CAR T-cell therapy were included. 
  • At Day 28 post CAR T-cell infusion, 31 patients achieved a minimal residual disease-negative CR. 
  • Grade 1–2 and Grade 3 cytokine release syndrome occurred in 94.1% and 2.9% of patients, respectively. 
  • No cases of immune effector cell-associated neurotoxicity syndrome were reported.
  • At 18 months post-transplant, the relapse incidence of patients with ≤20% vs >20% bone marrow blasts prior to CAR T-cell infusion was 0% and 30%, respectively (p = 0.006). 
  • There were no significant differences in OS, LFS, NRM, or RI by age group, interval time between CAR T-cell infusion to allo-HSCT, immunophenotype, or diagnosis. 

Outcomes after CD7 CAR T-cell therapy vs chemotherapy

  • A total of 124 patients achieved CR with chemotherapy alone prior to allo-HSCT; these patients were compared to those achieving CR with CD7 CAR T cells. 
  • There were no significant differences in 2-year OS, LFS, NRM, and relapse incidence rates between the two groups (Figure 1). 
  • There were no statistically significant differences in cumulative incidence of any-grade acute GvHD, chronic GvHD, or infections. 
  • Univariate and multivariate analyses showed that treatment with CD7 CAR T cells prior to allo-HSCT did not have a negative impact on transplantation outcomes. 
  • Patients aged >14 years had a lower LFS and OS but a higher NRM compared with patients aged <14 years. 

Figure 1. 2-year OS, LFS, NRM, and RI between CD7 CAR T-cell and chemotherapy groups*

CAR, chimeric antigen receptor; LFS, leukemia-free survival; NRM, non-relapse mortality; OS, overall survival; RI, relapse incidence. 
*Data from Cao, et al.1

 

Key learnings
  • Findings from this study suggest that allo-HSCT is safe and effective for patients with R/R T-ALL/LBL achieving a CR post CD7-directed CAR T-cell therapy. 
    • However, the sample size was small and larger studies are needed to confirm these findings.
  • Similar post-transplantation outcomes were observed for patients treated with CD7 CAR T-cell therapy and chemotherapy alone. 

References

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