META 10-19, an IL-10–expressing anti-CD19 CAR T-cell therapy, elicited an objective response rate (ORR) of 100% in patients with high-risk relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated at ultra-low doses, according to data from a first-in-human phase 1 study (NCT05715606) presented in a poster session at the
Among the 14 evaluable patients, 92.9% achieved a complete response, and 1 patient (7.1%) experienced a partial response. At a data cutoff of April 30, 2026, and a median follow-up of 27.4 months (range, 5.6-38.4), the median progression-free survival (PFS) had not been reached, with a 1-year PFS rate of 71.4%. The median overall survival (OS) also had not been reached, with a 1-year OS rate of 92.9%.
“This first-in-human trial of META 10-19, an IL-10–expressing, anti-CD19 CAR T-cell product, for the treatment of relapsed/refractory DLBCL exhibited [a] promising, manageable safety profile and durable efficacy at ultra-low doses in patients with high-risk features,” presenting study author Qianwen Xu, MD, of the University of Science and Technology in Hefei, China, and colleagues wrote in a poster presentation of the data.
Patients with high-risk features, including a high International Prognostic Index score, primary refractory disease, bulky disease, multiple extranodal involvement combined with nodal disease, and central nervous system (CNS) infiltration, generally exhibit poor response to CAR T-cell therapy and unfavorable prognosis, investigators wrote. The single-center phase 1 study evaluated META 10-19, a metabolically armored anti-CD19 CAR T-cell product engineered to autocrine IL-10, in patients with R/R DLBCL, most of whom presented with concurrent high-risk factors.
Eligible patients needed to have relapsed/refractory DLBCL that exhibited no response or progression after one standard chemotherapy regimen and one salvage therapy. At least one measurable lesion, adequate organ function, and an ECOG performance status of 0 or 1 for patients without CNS involvement was also required.
META 10-19 was administered at doses ranging from 0.002 × 10⁶ to 0.1 × 10⁶ CAR T cells/kg following a standard lymphodepletion regimen of fludarabine at 30 mg/m²/day for 3 days and cyclophosphamide at 300 mg/m²/day for 3 days. Safety and efficacy served as the primary objectives, with pharmacokinetics/pharmacodynamics as a secondary objective.
Of 19 eligible patients, 5 were withdrawn from the study prior to lymphodepletion chemotherapy due to unstable medical conditions; 14 received META 10-19 and completed safety and efficacy evaluation. Among the treated patients, high-risk characteristics included primary refractory disease (64.3%), combined nodal and extranodal disease (42.9%), bulky disease (14.3%), primary CNS lymphoma (35.7%), and secondary CNS lymphoma (7.1%).
The study enrolled a population enriched for CNS disease, with primary CNS lymphoma in 35.7% of treated patients and secondary CNS lymphoma in 7.1%. Responses were sustained across the follow-up period, with PFS and OS curves plateauing beyond 30 months in the overall population.
Pharmacokinetic analysis of META 10-19 demonstrated CAR T-cell expansion following infusion, with peak CAR copies observed within the first months and evidence of late re-expansion in a subset of patients.
The chemotherapy-free bispecific and CAR T-cell options that have reshaped later-line R/R DLBCL continue to expand; epcoritamab-bysp (Epkinly) plus lenalidomide (Revlimid) recently improved PFS vs rituximab (Rituxan) plus gemcitabine and oxaliplatin in the phase 3 EPCORE DLBCL-4 trial (NCT06508658) in patients with R/R DLBCL who had received at least 1 prior line of therapy.2
Any-grade cytokine release syndrome (CRS) occurred in 100% of treated patients, but was grade 3/4 in only 7.1%. Immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in 14.3% of patients, all of which were grade 3/4. Immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS) occurred in 42.9% of patients, with no grade 3/4 events.
Any-grade anemia, neutropenia, and thrombocytopenia occurred in 100%, 100%, and 92.9% of patients, respectively; the corresponding grade 3/4 rates were 71.4%, 100%, and 85.7%. Any-grade increased alanine aminotransferase levels was reported in 35.7% of patients, including 28.6% at grade 3/4.
