Base edited CD7 CAR T-cell therapy for childhood R/R T-ALL: preliminary results from a phase I trial

The survival outcomes for patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) are poor; therefore, there is a need for novel targeted therapies in this patient population.

Here, we summarize preliminary results of a phase I trial (EudraCT:2021-004312-25) evaluating the efficacy and safety of CD7-directed chimeric antigen receptor (CAR) T-cell therapy in children with R/R T-cell ALL, presented by Chiesa at the 50th Annual Meeting of the EBMT.

Study design¹

This was an open-label, single-center phase I study including patients aged 6 months to 16 years with R/R CD7+ (>99%) T-cell malignancies and bone marrow involvement who were eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT).

• The treatment schema is outlined in Figure 1
• The primary endpoint was safety
• Secondary endpoints included
  • disease remission by Day 28;
  • 1-year overall survival and disease-free survival;
  • time and duration of remission;
  • expansion, persistence, and elimination of base-edited CAR T-cells; and
  • side effects.

Figure 1. Treatment schema* 

Allo-HSCT, allogeneic hematopoietic stem cell transplantation; BM, bone marrow; CAR, chimeric antigen receptor; MRD, minimal residual disease.
*Data from Chiesa.^1
†Dose: 0.2−2.0 × 10⁶ per kilogram; max: 5 × 10⁴ per kilogram TCRαβ T cells

Key findings^1,2

• A total of 10 patients were included in the study
• Patient 1 with refractory T-ALL underwent a bone marrow transplantation from a 10/10 matched-unrelated donor after total body irradiation/etoposide conditioning
  • experienced early relapse at 6 weeks post-HSCT
  • had 9% disease prior to lymphodepletion
• Patient 2 had refractory T-ALL and 80% blasts prior to lymphodepletion
• Patient 3 had bone marrow and central nervous system relapsed T-ALL following two allo-HSCTs
• The outcomes for the three patients who subsequently received base-edited CD7-directed CAR T-cell therapies are summarized in Figure 2

Figure 2. Outcomes of CD7-directed CAR T-cells in children with R/R T-ALL*

CAR, chimeric antigen receptor; CMV, cytomegalovirus; CNS, central nervous system; CR, complete remission; HSCT, hematopoietic stem cell transplantation; ICANS, immune effector cell-associated neurotoxicity syndrome; IR, immune reconstitution; MRD, minimal residual disease; PCR, polymerase chain reaction; T-ALL, T-cell acute lymphoblastic leukemia.

*Data from Chiesa.¹