Published in:
Open Access
01-12-2023 | Acute Lymphoblastic Leukemia | Research
Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia
Authors:
Yue Tan, Lingling Shan, Liping Zhao, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Zhenglong Tian, Yibing Zhang, Jiecheng Zhang, Alex H. Chang, Xiaoming Feng, Jing Pan
Published in:
Journal of Hematology & Oncology
|
Issue 1/2023
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Abstract
Background
Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up.
Methods
Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 × 106 (± 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes.
Results
Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0–29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0–10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8–59.8%) and 42.3% (95% CI, 18.8–65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7–12.5) months and 18.3 (95% CI, 12.5–20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3–4 cytokine release syndrome (CRS; 10%) and grade 1–2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants.
Conclusions
In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event.
Trial registration
ChiCTR2000034762.