Introduction
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive CD4⁺ T-cell malignancy linked to HTLV-1 infection, with limited therapeutic options and poor prognosis. CD70 is aberrantly expressed in ATLL and promotes immune evasion via CD27 signaling, making it a rational therapeutic target. CTX130 is an allogeneic, CRISPR-Cas9–engineered CAR-T therapy directed against CD70, designed as an alternative to autologous products. We report safety, efficacy, and genomic findings from six pretreated ATLL patients treated with CTX130 in the Phase 1 COBALT-LYM trial.
Methods
This single-arm, open-label study enrolled patients with relapsed or refractory T-cell malignancies in the USA, Australia, and Canada. Eligible patients received ≥1 prior therapy and had ECOG 0–1. Lymphodepletion with fludarabine and cyclophosphamide preceded CTX130 infusion; repeat dosing was allowed. The primary endpoint was safety; secondary endpoints included ORR, PFS, and OS. Four patients underwent NGS for mutational profiling and clonal dynamics.
Results
Between August 2020 and May 2023, six ATLL patients received CTX130, with follow-up through July 2025. Median age was 54 years (range, 33–72). Two patients (29%) had the acute/leukemic subtype and five (71%) had the lymphomatous subtype. CTX130 doses ranged from 3×10⁷ to 9×10⁸ CAR-T cells; three received a second infusion. No CRS or ICANS occurred. Grade ≥3 adverse events included infections and neutropenia. ORR was 50%, with two complete and one partial response. Median PFS was 2.5 months and mOS 7.8 months. Two patients remained alive, one exceeding 37 months. NGS revealed clonal shifts and a STAT3 mutation in a long-term responder, suggesting adaptive genomic remodeling under immune pressure.
Conclusions
CTX130 showed manageable safety and durable activity in ATLL, supporting CD70 as a viable therapeutic target.
