Efficacy and safety of Axicabtagene ciloleucel (Axi‐cel) for the treatment of relapse/refractory non‐Hodgkin lymphoma: First real‐world data in Chinese population

Abstract

Background: Axi-cel was approved by NMPA to treat R/R LBCL adult patients who had received 2 or more prior treatments in 2021 June. For better understanding the efficacy and safety of commercial Axi-cel in Chinese R/R NHL patients in real world setting, we conducted this multi-center, non-interventional study (ChiCTR2100047990). The accrual goal is 200 patients, and the primary endpoint is median OS. Here we made an interim analysis and reported clinical outcomes of Chinese patients treated by commercial CAR-T products in real world for the first time. Methods: R/R NHL patients treated with commercial Axi-cel in 17 authorized treatment centers from 11/2021 to 02/2023 were included. All patients signed written informed consents. We reported best objective response rate (bORR), best complete response (bCR) rate and adverse events. Results: A total of 101 R/R NHL patients were efficacy-evaluable. The median age was 56.8 years old, and 25 (24.8%) patients were ≥65 years. Fifty-nine patients were male. Baseline characteristics, including 80 (79.2%) with DLBCL, 4 (4.0%) with PMBCL, and 6 (5.9%) with high grade B-cell lymphoma. Forty-two (44.2%) patients had IPI ≥3 and 18 (24.3%) patients ECOG PS were ≥2. The median prior lines of therapy was 2, including 36 (35.6%) patients got ≥3 previous treatments and 10 patients had history of ASCT. Eighty-four patients were resistant to previous therapy, and the primary refractory subgroup reached 47 (46.5%). Bridging therapy was given in 56 (55.4%) patients, while combination therapy in 29 (28.7%) patients. The median follow-up was 9.2 months. The bORR and bCR was 83.2% (95% CI, 74.4 to 89.9) and 58.4% (95% CI, 48.2 to 68.1) respectively (Figure 1A). Response rates were consistent across key covariates, including disease type, disease stage, IPI score, cell-of-origin subtype, etc. Patients ≥65 years had favorable ORR [92.0% (95% CI, 74.0–99.0)] and CR rate [80.0% (95% CI, 59.3–93.2)]. Median PFS was 12.0 months (95% CI, 7.3 to NA). The median DOR and OS were not reached. No new safety signal was observed in Chinese patients. The most common ≥ grade 3AE were white-cell count decreased (in 87.6% of the patients), neutropenia (in 82.9%), pyrexia (in 73.3%). Eighty-one patients experienced cytokine release syndrome (CRS) of any grade, and 16 (15.2%) patients occurred grade 3 or higher. Any grade of neurologic events (NE) occurred in 17 (16.2%) patients, and only 1 (1.0%) patients were grade 4. No grade 5 CRS or NE appeared (Figure 1B-C). Fifty-five percent received tocilizumab and 52% received glucocorticoids to manage CRS and/or NE. The median cumulative cortisone-equivalent corticosteroid dose was 2000 mg, which was similar to ZUMA-1 cohort6 and much smaller than ZUMA-1 cohort1+2. The research was funded by: The research was funded by Fosun Kite Biotechnology Co., Ltd., Shanghai, China. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies No conflicts of interests pertinent to the abstract.