LBA1 - IL-10 expressing CD19 CAR-T cells induce complete remission and improve long-term protection in relapsed or refractory B-cell hematological malignancies

Background

Meta10-19, the innovative IL-10 expressing CD19 CAR-T cells, show significant potential in addressing T cell dysfunction, a major hurdle in current CAR-T therapies. This dysfunction often leads to resistance and relapse in patients with relapsed/refractory (r/r) B-cell hematological malignancies.

Methods

From February 2023 to July 2024, we enrolled and treated a total of 20 eligible patients with r/r B-cell hematological malignancies, including 10 patients with DLBCL and 10 patients with B-ALL. Patients received a single infusion of Meta10-19 across multiple dose level (DL) cohorts from 2.0×10⁴ cells/kg to 2.0×10⁵ cells/kg. The administration followed a standard lymphodepletion regimen involving 30 mg/m²/day fludarabine for 3 days, and 300 mg/m²/day cyclophosphamide for 3 days. CRS and ICANS were graded according to Lee 2014 and ASTCT 2019 guidelines, respectively. AEs were assessed based on CTCAE 5.0 criteria.

Results

As of July 16, 2024, Meta10-19 had been successfully infused into 20 eligible patients, who subsequently underwent comprehensive safety and preliminary efficacy evaluations. The median age of the cohort was 50 years (range 17-65). Remarkably, the complete response (CR) rate for all 20 patients was 100% (20/20) and maintained at 94.11% at 6 months (16/17) post-treatment, which is much higher than commercial products (approximately 50%). Notably, 5 patients have been surviving over 12 months, with the longest observed remission duration to date being 17 months. Treatment-related AEs, predominantly neutropenia, thrombocytopenia, and anemia, were manageable and effectively resolved with standard and supportive care.

Clinical trial identification

NCT06277011

Legal entity responsible for the study

Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China

Funding

Leman Biotech Co., Ltd. Shenzhen, China

Disclosure

All authors have declared no conflicts of interest.