Chinese medical journal · 2025
Long-term outcomes of CNCT19 chimeric antigen receptor T-cell therapy in relapsed or refractory aggressive B-cell lymphoma.
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Liu Wei, Xie Ting, Zhang Zhuoxin, Huang Wenyang, Liu Huimin, Sui Weiwei, Deng Shuhui, Lyu Rui, Wang Yi, Wang Qi, Xiong Wenjie, Xu Yan, Lyu Lulu, Ma Yueshen, Qiu Lugui, Wang Jianxiang, Zou Dehui
Аннотация
BACKGROUND: Most anti-CD19 chimeric antigen receptor (CAR) T-cell products have the single-chain variable fragment (scFv) derived from the FMC63 monoclonal antibody. We developed a new hybridoma clone, HI19α, which binds to distinct epitopes on CD19. CNCT19 is a second-generation CAR T-cell with a scFv derived from clone HI19α and a 4-1BB costimulatory domain. A pilot clinical trial was conducted to assess the safety and preliminary efficacy of CNCT19 cells (CNCT19s) in patients with relapsed or refractory (R/R) aggressive B-cell lymphoma.
METHODS: From June 2017 to March 2019, 16 patients with R/R CD19-positive aggressive B-cell lymphoma from the Institute of Hematology and Blood Disease Hospital were enrolled. All patients received lymphodepleting chemotherapy with fludarabine (25-30 mg/m 2 /per day on days 4, 3, and 2) and cyclophosphamide (350 mg/m 2 /per day on days 4 and 2) before CNCT19s infusion. The primary objective was the safety profiles. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.
RESULTS: The study cohort comprised 14 patients diagnosed with de novo diffuse large B-cell lymphoma (DLBCL), one patient with follicular lymphoma grade 3B (FL3B), and one patient with Richter's transformation. The patients had received a median of 3 (range 1-7) lines of prior therapy. Thirteen patients (81.3%) had disease resistant to the last-line therapy, and TP53 mutation and/or deletion were detected in 5 of 12 patients (41.7%). The median dose of CNCT19s infusion was 3.6 × 10 6 (range 1.8-6.5 × 10 6 )/kg. Cytokine release syndrome occurred in 11 (68.8%) patients, all classified as grade 1. One patient (6.3%) experienced CAR T-cell-related encephalopathy syndrome. The overall response rate and the complete response rate were 75% (12/16) and 43.8% (7/16), respectively. After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, respectively.
CONCLUSIONS: CNCT19s exhibited favorable safety profiles and efficacy in patients with R/R DLBCL and FL3B. Long-term follow-up confirmed the curative potential of CNCT19s in R/R aggressive B-cell lymphoma.
TRIAL REGISTRATION: ClinicalTrials.gov , NCT03029338.
METHODS: From June 2017 to March 2019, 16 patients with R/R CD19-positive aggressive B-cell lymphoma from the Institute of Hematology and Blood Disease Hospital were enrolled. All patients received lymphodepleting chemotherapy with fludarabine (25-30 mg/m 2 /per day on days 4, 3, and 2) and cyclophosphamide (350 mg/m 2 /per day on days 4 and 2) before CNCT19s infusion. The primary objective was the safety profiles. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.
RESULTS: The study cohort comprised 14 patients diagnosed with de novo diffuse large B-cell lymphoma (DLBCL), one patient with follicular lymphoma grade 3B (FL3B), and one patient with Richter's transformation. The patients had received a median of 3 (range 1-7) lines of prior therapy. Thirteen patients (81.3%) had disease resistant to the last-line therapy, and TP53 mutation and/or deletion were detected in 5 of 12 patients (41.7%). The median dose of CNCT19s infusion was 3.6 × 10 6 (range 1.8-6.5 × 10 6 )/kg. Cytokine release syndrome occurred in 11 (68.8%) patients, all classified as grade 1. One patient (6.3%) experienced CAR T-cell-related encephalopathy syndrome. The overall response rate and the complete response rate were 75% (12/16) and 43.8% (7/16), respectively. After a median follow-up of 54.0 months, the estimated 5-year progression-free survival and overall survival rates were 25.0% and 37.5%, respectively.
CONCLUSIONS: CNCT19s exhibited favorable safety profiles and efficacy in patients with R/R DLBCL and FL3B. Long-term follow-up confirmed the curative potential of CNCT19s in R/R aggressive B-cell lymphoma.
TRIAL REGISTRATION: ClinicalTrials.gov , NCT03029338.