Why This Study Matters
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, accounting for roughly 25% of all NHL cases worldwide. While first-line chemoimmunotherapy cures up to half of patients who achieve a complete remission, those who relapse or remain refractory face a difficult treatment path. CD19-directed CAR T-cell therapy has transformed care for this group, but toxicity — particularly cytokine release syndrome (CRS) and neurotoxicity — and durability of response remain active areas of engineering and investigation.
This Phase 1 study evaluates META 10-19, a CD19 CAR T-cell product engineered to also express interleukin-10, a cytokine reported to help CAR T cells resist functional exhaustion, delivered at ultralow cell doses in patients with relapsed/refractory DLBCL.
Study Design
This was a nonrandomized, single-arm, dose-exploration Phase 1 trial conducted at a single site, the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou, China. Patients were enrolled between November 16, 2023, and April 7, 2025, with a data cutoff of January 20, 2026. Following lymphodepleting chemotherapy with fludarabine and cyclophosphamide, patients received META 10-19 at one of three dose levels, ranging from 2 × 10³ to 2 × 10⁴ CAR T cells/kg. Primary endpoints were adverse events, dose-limiting toxic effects, and objective response rate (ORR); secondary endpoints were complete remission rate and cellular kinetics of META 10-19.
Patient Population
Of 20 patients screened, 13 received a META 10-19 infusion and were evaluable for this analysis. The treated population had a median age of 61 years (range, 35–74) and included 8 men (61.5%) and 5 women (38.5%). Median follow-up at data cutoff was 15.6 months (range, 0.7–25.5 months).
Primary Endpoint Results
Among the 13 treated patients, the objective response rate was 92.3%, comprising complete remission in 11 patients (84.6%) and partial remission in 1 patient (7.7%). One patient died prior to response assessment due to disease-related gastrointestinal complications; the published abstract does not attribute this death to a specific treatment-related adverse event grade. At data cutoff, 5 of the 13 treated patients had a maintained complete remission, while 7 patients experienced disease relapse or progression, including 2 cases of CD19-negative relapse.
Subgroup Analyses
| Subgroup | Reported Finding |
|---|---|
| All treated patients | The published abstract does not report subgroup-level statistical results — for example by dose level, age group, or prior lines of therapy. It notes only qualitatively that CAR T-cell expansion was robust across dose levels, without dose-specific numeric breakdowns. No subgroup hazard ratios, confidence intervals, or p-values are available and none have been estimated to fill this gap. |
Safety Profile
Toxicity in this ultralow-dose cohort was weighted toward lower-grade events. Cytokine release syndrome (CRS) occurred in 92.3% of patients (12 of 13) — 8 grade 1, 3 grade 2, and 1 grade 3, with no grade 4 or 5 events reported. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 15.4% of patients (2 of 13) — 1 grade 1 and 1 grade 2, also with no grade 4/5 events. One on-study death occurred (disease-related gastrointestinal complications, prior to response assessment) and is not characterized in the abstract as a treatment-related adverse event of a specific grade.
| Adverse Event | Any Grade | Grade 1 | Grade 2 | Grade 3 | Grade 4/5 |
|---|---|---|---|---|---|
| Cytokine release syndrome (CRS) | 12/13 (92.3%) | 8 | 3 | 1 | 0 reported |
| Immune effector cell-associated neurotoxicity syndrome (ICANS) | 2/13 (15.4%) | 1 | 1 | 0 | 0 reported |
Interpretation and Broader Context
Ultralow-dose META 10-19 demonstrated promising antitumor activity and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma.
— Verbatim from the study abstract (Hu et al., JAMA Oncology, 2026)
These early Phase 1 results suggest an ultralow-dose, IL-10-armored CD19 CAR T-cell approach can achieve a high response rate in a small, heavily pretreated cohort, with a safety profile weighted toward lower-grade CRS and ICANS events. For context, the FDA-approved standard CD19 CAR T-cell product axicabtagene ciloleucel reported an objective response rate of 83% (58% complete response) in refractory large B-cell lymphoma in its 5-year ZUMA-1 follow-up — a different trial, offered here only as a cross-study benchmark rather than a head-to-head comparison. Because META 10-19 has been studied in only 13 patients at a single center without a comparator arm, any comparison to standard-dose CAR T-cell products should be considered hypothesis-generating rather than definitive.
The abstract reports that 2 of the 7 relapsing patients had CD19-negative relapses; it does not further characterize the mechanism behind this finding, and no external source specific to this trial was identified to elaborate on it further, so it is presented here strictly as reported.
Future Directions
The study authors state that further investigation in larger cohorts is warranted to confirm efficacy and safety and to better characterize durability of response, including the mechanisms underlying CD19-negative relapse observed in this cohort.
In a 13-patient, single-center Phase 1 trial, ultralow-dose META 10-19 — a CD19 CAR T-cell product also engineered to express interleukin-10 — produced an objective response rate of 92.3% and a complete remission rate of 84.6% in heavily pretreated relapsed/refractory DLBCL, with cytokine release syndrome weighted toward lower grades and no grade 4/5 CRS or ICANS reported. At data cutoff, 5 of 13 patients remained in complete remission while 7 had relapsed or progressed, including 2 with CD19-negative disease. These are small, single-arm, single-center data without a comparator arm; durability, mechanism of CD19-negative relapse, and confirmation in larger cohorts all remain to be established.