Abstract Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical
Background: Autologous CD-19 directed chimeric antigen receptor(CAR) T-cell therapy has become the standard of care of R/R LBCL patients who had received 2 or more prior lines of therapy1. Axi-cel was approved to treat these patients by NMPA in 2021 June2. 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)3. The accrual goal is 200 patients, and the primary endpoint is mOS.
Aims: 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 rate (bCR) and adverse events of special interest (AESI) including cytokine release syndrome (CRS) and neurologic events(NE).
Results: A total of 101 R/R NHL patients were efficacy-evaluable. The median age was 56.8 (23,80) years old, and 25 (24.8%) patients were ≥65 years. Fifty-nine patients were male. Baseline characteristics of these patients, including 80 (79.2%) with DLBCL, 4 (4.0%) with PMBCL, and 6 (5.9%) with high grade B-cell lymphoma. More than 30% patients had IPI ≥3 and 7 patients ECOG PS were ≥2. The median prior lines of therapy was 2, including 36 (35.6%) patients got ≥3 previous treatment. Eighty-four patients were resistant to previous therapy, and the primary refractory subgroup reached 47 (46.5%). Five patients relapsed after ASCT. 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 1). Response rates were consistent across key covariates, including disease type, disease stage, IPI score, cell-of-origin subtype and use of bridging therapy and combination therapy. 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. The 12m-OS rate was estimated to be 84.3% (95% CI, 74.2 to 90.7).No new safety signal was observed in Chinese patients. The most common AE of grade 3 or higher were white-cell count decreased (in 87.6% of the patients), neutropenia (in 82.9%), pyrexia (in 73.3%). Eighty-one patients experienced CRS of any grade, and 16 (15.2%) patients occurred grade 3 or higher. Any grade of NE occurred in 17 (16.2%) patients. Of note, only 1 (1.0%) patients were grade 4. No grade 5 CRS & NE appeared. Fifty-five percent received tocilizumab and 52% received glucocorticoids to manage CRS and/or NE. The median cumulative cortisone-equivalent corticosteroid dose was 2000mg, which was similar to ZUMA-1 cohort6 and much smaller than ZUMA-1 cohort1 + 2. Summary/Conclusion:
This interim analysis showed global consistent efficacy of Axi-cel in Chinese R/R NHL patients, while NE of any grade and grade 3 or higher were lower.
References：1. NCCN Guidelines Version 1.20232.https://www.nmpa.gov.cn/yaowen/ypjgyw/20210623094232187.html3. https://www.chictr.org.cn/hvshowproject.aspx?id=148716
Keywords: Real world data, CD19, NHL, CAR-T