Safety and efficacy of donor-derived anti-CD19 CAR T-cell therapy for R/R B-ALL post-allo-HSCT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective treatment options for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, relapse post-allo-HSCT is common and associated with poor prognosis and limited treatment options. Strategies to treat B-ALL after transplant relapse are needed.

Recently, Luo et al.¹ published results in eClinicalMedicine from a single arm, phase I trial (NCT04516551) investigating the efficacy and safety of GC007g, a donor-derived anti-CD19 CAR T-cell therapy, for the treatment of patients with relapsed/refractory B-ALL who have relapsed after allo-HSCT. We summarize the key results below.

Study design¹

• Included patients aged 18–70 years with B-ALL who have relapsed post-allo-HSCT and an Eastern Cooperative Oncology Group status of ≤1.
• Treatment consisted of a single dose of GC007g infusion at 2 dose levels:

• 6 × 10⁵/kg CAR T cells, or
• 2 × 10⁶ /kg CAR T cells.

• The primary objective was safety, including the incidence of dose-limiting toxicity and adverse events.
• Secondary objectives included overall response rate, progression-free survival (PFS), and overall survival (OS).

Key findings¹

• A total of nine patients successfully received GC007g infusion at:

• 6 × 10⁵/kg (n = 3); or
• 2 × 10⁶ /kg (n = 6).

• The median time from leukapheresis to infusion was 33 days
• The median follow-up time was 475 days
• At 28 days post infusion, eight patients achieved a complete response with incomplete count recovery, while one patient achieved a complete response.
• All patients achieved undetectable measurable residual disease.
• All patients achieved an overall response at 3 months post infusion (Figure 1).

ORR, overall response rate.
*Adapted from Luo, et al.¹

• The estimated 1-year OS rate was 85.7%
• The estimated 1-year PFS rate was 77.8%
• The median OS, PFS, and duration of response was not reached
• One patient experienced a dose-limiting toxicity at 4 days post infusion
• All patients experienced cytokine release syndrome
  • Overall, 89% of cases were Grade 1/2 with Grade 3 cytokine release syndrome reported in one patient
• There were no cases of immune effector cell-associated neurotoxicity syndrome
• Grade ≥3 hematologic adverse events were experienced by all patients:
  • Neutropenia (n = 9)
  • Lymphocytopenia (n = 7)
  • Thrombocytopenia (n = 2)
  • Anemia (n = 3)

Key learnings

Results from this study show that donor-derived CAR T-cell therapy is well tolerated, clinically feasible, and can mediate antitumor effect in patients who have relapsed post-allo-HSCT. GC007g is due to undergo further assessment in an expansion cohort of patients with B-ALL who have relapsed after allo-HSCT.