CAR T CELL THERAPY achieved high response rates at ultralow doses in adults with relapsed or refractory diffuse large B cell lymphoma, according to findings from a phase one clinical trial. Investigators reported encouraging antitumour activity alongside a manageable safety profile, supporting further evaluation of the treatment in larger patient cohorts.
The nonrandomised phase one trial enrolled patients at a single centre between November 2023 and April 2025. Of 20 patients screened, 13 received an infusion of interleukin (IL) 10 expressing CD19 CAR T cells following lymphodepletion with fludarabine and cyclophosphamide. Patients received one of three ultralow dose levels of 2×10³, 5×103, and 2×10⁴ CAR T cells per kilogram. The median follow up was 15.6 months.
The primary study endpoints were adverse events, dose limiting toxic effects, and objective response rate. Secondary endpoints included complete remission and cellular expansion of the infused CAR T cells.
Among the 13 treated patients, the objective response rate was: 92.3%. Complete remission was achieved in 11 patients: 84.6%, while one patient achieved partial remission: 7.7%. One patient died before response assessment because of disease related gastrointestinal complications.
Cytokine release syndrome occurred in 12 patients and was predominantly low grade, including grade 1 events in eight patients and grade 2 events in three patients. One patient experienced grade 3 cytokine release syndrome. Immune effector cell associated neurotoxicity syndrome developed in two patients, with one grade 1 event and one grade 2 event.
Investigators also observed robust expansion of the infused cells across all dose levels, with a median peak expansion of: 660.7 cells/µL; range: 30.7–10,562.3 cells/µL.
At the data cutoff, five patients remained in complete remission, while seven experienced relapse or disease progression, including two with CD19 negative relapse.
The findings suggested that ultralow dose IL 10 expressing CD19 CAR T cells produced substantial antitumour activity with manageable toxicity in patients with relapsed or refractory diffuse large B cell lymphoma. The investigators concluded that larger studies are required to confirm the safety and efficacy of this approach and to better define the durability of clinical responses.
Reference
Hu Y et al. Antigen receptor t cells in relapsed/refractory diffuse large b-cell lymphoma: a nonrandomized clinical trial. JAMA Oncol. 2026;doi: 10.1001/jamaoncol.2026.2490.
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