IL-10-expressing, anti-CD19 CAR T cells for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: an open-label, single-arm, phase 1 study
Mené sur 15 patients atteints d'une leucémie lymphoblastique aiguë à cellules B, réfractaire ou récidivante (âge : 3-70 ans), cet essai de phase I détermine la dose maximale tolérée de META 10-19, une immunothérapie à base de lymphocytes CAR-T ciblant CD-19 et exprimant IL-10, puis évalue son efficacité du point de vue du taux de réponse
Background: Although chimeric antigen receptor (CAR) T-cell therapy has improved clinical outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, treatment resistance and relapse after remission driven by CAR T-cell dysfunction remain significant clinical challenges. To mitigate this limitation, we developed anti-CD19 CAR T cells expressing IL-10 (META 10-19) and aimed to assess their safety and activity in this patient group.
Methods: We conducted an open-label, single-arm, phase 1 study at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China. Patients aged 3–70 years with relapsed or refractory B-cell acute lymphoblastic leukaemia diagnosed according to the 5th edition of WHO's Classification of Haematolymphoid Tumours and an Eastern Cooperative Oncology Group performance status score of 0–1 were eligible for inclusion. Lymphodepletion was achieved by use of intravenous fludarabine (25–30 mg/m2 per day) and intravenous cyclophosphamide (250–300 mg/m2 per day) from day –5 to –3. META 10-19 was administered intravenously in a single infusion of 0·1 × 106 or 0·2 × 106 CAR T cells per kg. The primary endpoints were safety, assessed by dose-limiting toxicity, immune effector cell-associated toxicity, and other treatment-related adverse events; and activity, assessed by clinical response rate and survival. Safety and activity were analysed in all eligible patients who received META 10-19 infusion. This study is registered with ClinicalTrials.gov, NCT05747157, and has been completed.
Findings: Between May 16, 2023, and July 29, 2024, 15 patients were enrolled and underwent whole-blood collection. 12 patients (median age 48 years [IQR 33–53]) received META 10-19 infusion and were included in the analyses, of whom all patients were Chinese, seven (58%) were men, and five (42%) were women. Median follow-up was 12·5 months (IQR 7·4–15·6). The most common grade 3 or worse adverse events were haematological toxicities in all 12 (100%) patients, including neutropenia (12 [100%]), anaemia (ten [83%]), and thrombocytopenia (ten [83%]). 11 (92%) patients had grade 1 or 2 cytokine release syndrome; no patients experienced immune effector cell-associated neurotoxicity syndrome. No treatment-related deaths were reported. Overall response at 1 month was observed in all 12 (100%) patients, with complete response in four (33%) patients, complete response with incomplete or partial haematological recovery in five (42%) patients, and morphological leukaemia-free state in three (25%) patients.
Interpretation: META 10-19 showed a manageable safety profile and promising antileukaemic activity in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia at low doses, highlighting that IL-10 engineering is a potential strategy for optimising CAR T-cell therapy in this patient group.
The Lancet Haematology , résumé, 2025