Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma in Chinese population: A single-arm, multicenter, phase 2 trial

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.