Donor-Derived CD7 CAR T-Cell Therapy Demonstrated Durable Efficacy Among Subset of Patients With R/R T-Cell ALL

Results from a 2-Year Follow-Up Phase 1 Study

According to a 2-year follow-up of a phase 1 trial recently published in the Journal of Hematology & Oncology, donor-derived CD7 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable efficacy among a subset of patients with relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL). In cases where treatment failed, the primary cause was disease relapse and severe infection. 

Yue Tan, Beijing Gobroad Boren Hospital, Beijing, China, and coauthors stated, “Developing therapeutic CAR T-cell treatments for T-ALL is particularly challenging because most validated CAR targets are also expressed on normal T cells.” They explained that this treatment may lead to the risk of “tumor contamination, fratricide of CAR T cells, and the depletion of healthy T cells.” 

However, there has been previous evidence that indicates when T-cells are collected from allogeneic donors with retention of CD7 molecules in the endoplasmic reticulum, risks may be avoided. The study authors aimed to assess the safety and efficacy of donor-derived CD7 CAR T-cell therapy among patients with R/R T-ALL to test this further. 

The primary endpoint was safety, including the measurement of dose-limiting toxicities within 21 days and the occurrence of adverse events within 30 days. Secondary end points included the overall response rate, complete remission, progression-free survival, overall survival, and pharmacokinetics in peripheral blood.

20 patients with R/R T-ALL were enrolled in this trial and received CD7-directed CAR T-cells from previous stem cell transplantation donors, or newly HLA-matched donors after lymphodepletion. CD7-directed CAR T-cells were administered intravenously 1 × 106 (± 30%) cells per kg body weight on day 0. A lower dose, 5 × 105 (± 30%) cells per kg body weight, was permitted if the CAR T-cell product did not meet the target dose. 

Within 30 days after treatment, 10% of patients (n = 2) experienced grade 3 to 4 cytokine release syndrome, and 60% of patients (n = 12) experienced grade 1 to 2 graft-versus-host disease. 5 cases of infections and 1 case of grade 4 intestinal graft-versus-host disease occurred. Good CD7 CAR T-cell persistence was observed, but non-CAR T and natural killer cells predominantly lacked CD7 expression and returned to normal levels in 50% of patients. 

At a median follow-up of 27 months, the overall response rate was 95% (n = 19), with 85% of patients (n = 17) achieving a complete response. 35% of patients (n = 7) continued to stem cell transplantation. 6 patients experienced disease relapse at a median time of 6 months. 66% of the patients who experienced disease relapse (n = 4) were found to have lost CD7 expression on tumor cells. At 24 months, the progression-free survival was 36.8%, and the overall survival rate was 42.3%. In cases where treatment failed, the primary cause was disease relapse and late onset severe infection. 

In conclusion, results demonstrated that donor-derived CD7 CAR T-cell treatment exhibited durable efficacy among patients with R/R T-ALL. Strategies to prevent disease relapse and safety risks need to be investigated further. Dr Tan stated that this trial “provides valuable information for future design of CD7-targeted cellular therapy.” 

Source: 

Tan Y, Shan L, Zhao L, et al. Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia. J of Hem & Oncol. 5 April 2023;16(1). doi: 10.1186/s13045-023-01427-3