Phase 1 trial of ultralow-dose IL 10-expressing CAR T cells in relapsed/refractory diffuse large B-cell lymphoma

Interleukin 10-expressing CD19 CAR T cells (META 10-19) have demonstrated encouraging clinical activity in B-cell acute lymphoblastic leukemia, but their safety and efficacy in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) remain unknown. A phase 1 trial at the First Affiliated Hospital of Zhejiang University School of Medicine (China) evaluated META 10-19 in 13 patients with R/R DLBCL (median age 61 years, range 35-74; 8 men and 5 women). Following lymphodepletion with fludarabine and cyclophosphamide, patients received META 10-19 at dose levels 2x10³, 5x10³, or 2x10⁴ CAR T cells/kg. The primary endpoints were adverse events, dose-limiting toxic effects, and objective response rate. The median duration of follow-up was 15.6 months (range 0.7-25.5). The objective response rate was 92.3%, including complete response in 11 patients (84.6%) and partial remission in one patient (7.7%), while one patient died before response assessment because of disease-related gastrointestinal complications. CRS occurred in 12 patients (grade 1 in 8 patients, grade 2 in 3, and grade 3 in 1) and ICANS occurred in 2 patients (grade 1 in 1, grade 2 in 1). Robust in vivo CAR T-cell expansion was observed across dose levels, with a median peak expansion of 661 cells/μl (range 31-10 562). At data cutoff, 5 patients experienced maintained complete response and 7 experienced disease relapses or progression (2 with CD19 negative relapses). The authors conclude that the results of this trial suggest that ultralow-dose META 10-19 demonstrated promising antitumor activity and manageable safety in patients with R/R DLBCL.