In a nonrandomized phase I trial published in JAMA Oncology, ultra low–dose interleukin (IL)-10–expressing chimeric antigen receptor (CAR) T-cell therapy (META 10-19) appeared to be safe and active in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Hu et al noted that despite being administered at doses substantially lower than those used in conventional CAR T-cell therapy, META 10-19 achieved robust in vivo expansion and a high complete remission rate.
“IL-10 engineering has previously been associated with enhanced CAR T-cell persistence and antitumor activity in preclinical studies and B-cell acute lymphoblastic leukemia,” the investigators commented. “These findings extend prior observations to DLBCL and support further investigation of cytokine-engineered CAR T-cell strategies in B-cell malignant neoplasms.”
Study Details
This open-label, single-arm trial was conducted at the First Affiliated Hospital of Zhejiang University School of Medicine in China. After undergoing lymphodepletion with fludarabine and cyclophosphamide, 13 patients (median age = 61 years; 8 men [61.5%]) received META 10-19 at dose levels of 2 × 103, 5 × 103, or 2 × 104 CAR T cells/kg and were followed for a median of 15.6 months.
The investigators identified adverse events, dose-limiting toxic effects, and objective response rate as the primary endpoints. Secondary endpoints included complete remission and in vivo cellular kinetics of META 10-19.
Key Findings
The objective response rate was 92.3%, with 11 patients (84.6%) achieving a complete remission and 1 patient (7.7%) achieving a partial remission. One patient died of disease-related gastrointestinal complications before response assessment.
Twelve patients experienced cytokine-release syndrome (grade 1: n = 8; grade 2: n = 3; grade 3: n = 1), and two experienced immune effector cell–associated neurotoxicity syndrome (grade 1: n = 1; grade 2: n = 1).
The investigators observed robust in vivo CAR T-cell expansion across dose levels, with a median peak expansion of 660.7 cells/µL.
At data cutoff, complete remission was ongoing in five patients, whereas seven had experienced disease relapse or progression, including two with CD19-negative relapse.
“In this phase I nonrandomized clinical trial, ultra low–dose META 10-19 exhibited encouraging clinical activity, manageable safety profiles, and robust in vivo expansion in patients with relapsed or refractory DLBCL,” the investigators concluded. “These findings support further evaluation of cytokine-engineered CAR T-cell strategies in larger studies with extended follow-up.”
He Huang, MD, PhD, of the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, and Xingbing Wang, MD, PhD, of the First Affiliated Hospital of University of Science and Technology of China, Hefei, are the corresponding authors of the article in JAMA Oncology.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
