Ultralow-Dose Interleukin 10-Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell
Yongxian Hu1,2,3, Mingming Zhang1,2,3, Min Gao4,5
1Bone Marrow Transplantation Center of the First Affiliated Hospital and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
JAMA Oncology
|July 23, 2026
Summary
Ultralow-dose Interleukin-10 expressing CD19 chimeric antigen receptor (CAR) T cells (META 10-19) show promise for relapsed/refractory diffuse large B-cell lymphoma. This therapy demonstrated high response rates and a manageable safety profile in a phase 1 trial.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T cells, specifically Interleukin-10 (IL-10) expressing CD19 CAR T cells (META 10-19), have shown efficacy in B-cell acute lymphoblastic leukemia.
- The safety and efficacy of META 10-19 in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) were previously unknown.
Purpose of the Study:
- To evaluate the safety and efficacy of META 10-19 in patients diagnosed with R/R DLBCL.
- To determine the objective response rate and complete remission rates associated with META 10-19 treatment.
Main Methods:
- A nonrandomized, phase 1 clinical trial was conducted involving 13 patients with R/R DLBCL who received META 10-19 infusions.
- Patients received META 10-19 at dose levels of 2×10³, 5×10³, or 2×10⁴ CAR T cells/kg following lymphodepletion.
- Primary end points included adverse events, dose-limiting toxicities, and objective response rate, with secondary end points being complete remission and cellular kinetics.
Main Results:
- An objective response rate of 92.3% was observed, with 11 patients (84.6%) achieving complete remission (CR).
- Cytokine release syndrome occurred in 12 patients (grades 1-3), and immune effector cell-associated neurotoxicity syndrome occurred in 2 patients (grades 1-2).
- Robust in vivo CAR T-cell expansion was noted, with a median peak expansion of 660.7 cells/µL. At data cutoff, 5 patients maintained CR, while 7 experienced relapse or progression.
Conclusions:
- Ultralow-dose META 10-19 demonstrates promising antitumor activity and a manageable safety profile in patients with R/R DLBCL.
- These findings suggest that META 10-19 is a viable therapeutic option for R/R DLBCL.
- Further investigation in larger patient cohorts is warranted to confirm these results.
