Lineage Plasticity-Mediated Resistance to CD7-Directed CAR-T Therapy in Relapsed/Refractory T-ALL/LBL.

Authors

Jiahua Niu, Kun Wang, Shizhen Qiu, Fang Xiang, Huiying Qiu, Xueying Ding, Chongmei Huang, Jun Yang, Yin Tong, Yu Cai, Liping Wan, Kun Zhou, Jingwei Jiang, Baoxia Dong, Haopeng Wang, Xianmin Song

Published in

Transplantation and cellular therapy. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

CD7-directed chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL). However, relapse remains a major obstacle. We generated a recyclable CD7 CAR-T cells (CD7 CAR^Recyclable) and conducted a phase I clinical trial to evaluate its safety and response in patients with R/R T-ALL/LBL (NCT05290155). Fourteen patients received CAR-T cells and were evaluable for safety and response. Immunophenotypic and molecular profiling were performed longitudinally to characterize relapse patterns. Robust CAR-T expansion was observed in 13 of 14 patients (92.9%). Peak CAR-T concentration (Cmax) reached 62,389.69 copies/μg DNA (range: 3,175.94-326,482.67) at median 12 days post-infusion (range: 10-21). All patients experienced hematologic toxicities, and cytokine release syndrome occurred in 71.4% of patients, predominantly grade 1-2. While ICANS developed in 2 patients (14.3%, grade 2 and 3) at day 8 and 28, respectively. Three out of four patients achieved measurable residual disease (MRD) -negative complete remission in bone marrow, while the objective response rate for extramedullary disease was 78.6%. With a median follow-up of 8.5 months, the estimated 6-month overall survival (OS) and progression-free survival (PFS) were 62.3% and 44.6%, respectively. Notably, lineage switch relapse occurred in two patients with ETP-immunophenotype following CAR-T therapy. These findings suggest that lineage plasticity might represent an under-recognized mechanism of resistance to CD7-directed CAR-T therapy in T-ALL/LBL, particularly in ETP-ALL/LBL, warranting further exploring.

PMID:
42810712
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.