Anti-CD7 CAR-T cell therapy (Yake Biotechnology)

While the use of chimeric antigen receptor‐T (CAR‐T) therapy for T‐cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long‐term remission for patients with refractory/relapsed (R/R) T‐cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T‐ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T‐ALL 35, T‐LBL 25) received a single dose of naturally selected anti‐CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105/kg), a medium dose (1 to 1.5 × 106/kg), and a high dose (2 × 106/kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2‐year overall survival and progression‐free survival (PFS) were 63.5% (95% CI 47.7–79.4) and 53.7% (95% CI, 38.9–68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1‐year PFS 67.2% (95% CI 51.9–82.4) versus 15.0% (95% CI 0–40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR‐T therapy is effective in treating R/R T‐ALL/LBL patients with promising PFS while maintaining a manageable safety profile.