Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma in Chinese population: A single-arm, multicenter, phase 2 trial
Year: 2025
Type: conference-abstract
Abstract: Backgroud: Relapsed or refractory (R/R) indolent non-Hodgkin lymphomas (iNHLs) are incurable diseases. Based on the ZUMA-5 study, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, has been approved by the FDA for the treatment of adult patients with R/R follicular lymphoma (FL). Axi-cel was approved in China by the NMPA in June 2021 for the treatment of adult patients with R/R large B-cell lymphoma (LBCL). The efficacy and safety results of axi-cel for the treatment of R/R iNHLs including FL in the Chinese population have not yet been explored. Therefore, we conducted this single-arm, multi-center, phase 2 trial (ChiCTR2200058587) in China. AIMS: To assess the efficacy and safety of Axi-cel in R/R iNHLs in Chinese population. Methods: Patients were eligible if they were aged 18 years or older, with histologically confirmed iNHLs (FL or marginal zone lymphoma [MZL]), had relapsed or refractory disease, previously had two or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. The primary endpoint was best objective response rate (bORR) per Lugano classification. Secondary endpoints included complete remission (CR) rate, partial remission (PR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: As of data cutoff (August 16, 2024), 31 patients were enrolled (FL: 30, MZL: 1) and 28 patients (FL: 27, MZL: 1) were evaluable for efficacy (1 FL patient receiving low-dose axi-cel was not included). The median age was 53 years (range 33–71). 92.9% had stage III-IV disease. Progression of disease within 2 years of frontline chemoimmunotherapy (POD24) occurred in 64.3% of patients. Patients had a median 3 prior lines of therapy (range 2–9); 60.7% patients were refractory to last therapy; 29.6% FL patients had higher FLIPI scores. Median follow-up was 12.16 mo (90% CI 9.53, 15.08). 27 (96.4% [95% CI 84.15, 99.82]) of 28 patients had a bORR as assessed by investigators, including 26 (96.3% [95% CI 83.60, 99.81]) of 27 patients with FL and 1 (100%) with MZL. 20 (71.4%) of 28 patients had a complete response as assessed by investigators, including 19 (70.4%) of 27 patients with FL and 1 (100%) with MZL. The median time to response (TTR) and time to complete response (TTCR) were 1.02 mo (IQR 0.95-1.05) and 1.03 mo (IQR 1.00-2.97), respectively. Pharmacokinetic results showed that after analyzing 29 subjects from all groups combined, the median Tmax of anti-CD19 CAR-T cells in peripheral blood was 11 days (range 6-14) post-infusion, and the median Cmax was 35.81 cells/ μ L (IQR 6.70-103.35). No new safety signals were observed in the Chinese population. Cytokine release syndrome(CRS) of any grade occurred in 21 patients (72.4%), with 2 patients (6.9%) experiencing grade ≥3. Neurological events(NE) of any grade occurred in 16 patients (55.2%), with 2 patients (6.9%) experiencing grade≥3. No grade 5 CRS or NE appeared. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were decreased neutrophil count (86.2%), decreased white blood cell count (86.2%), and decreased lymphocyte count (17.2%). Summary/Conclusion: Axi-cel demonstrated deep responses in heavily pretreated Chinese patients with R/R iNHL; bORR was 96.4% with CR rate of 71.4%. Axi-cel had a generally manageable safety profile with a low incidence of grade ≥3 CRS or NE.
Source: Blood
Authors: Zhengming Jin, Huilai Zhang, Changju Qu, Wenbin Qian, Keshu Zhou, Wenrong Huang, Bing Xu, Hongmei Jing, Wenyu Li, Kang Yu, Ting Niu, Wei LIU, Xi Zhang, Yuhua Li, Huiqiang Huang, Haiyan Yang, Hua Yang, Wei Xu, Jinghua Zhao, Depei Wu
Institutions: First Affiliated Hospital of Soochow University, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Second Affiliated Hospital of Zhejiang University, Zhejiang University, Henan Cancer Hospital, Chinese PLA General Hospital, Chinese People's Liberation Army, Xiamen University, First Affiliated Hospital of Xiamen University, Peking University Third Hospital, Guangdong Provincial People's Hospital, Wenzhou Medical University, First Affiliated Hospital of Wenzhou Medical University, West China Hospital of Sichuan University, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, Army Medical University, Xinqiao Hospital, Zhujiang Hospital, Southern Medical University, Sun Yat-sen University Cancer Center, Zhejiang Cancer Hospital, University of Hong Kong - Shenzhen Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417004060
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