Efficacy and Safety of Axicabtagene Ciloleucel (Axi-cel) for the Treatment of Relapse/Refractory Non-Hodgkin's Lymphoma: Real-World Data in Chinese Population

Background: To better understand the efficacy and safety of commercial Axi-cel in Chinese relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL) patients in a real-world setting, we conducted this multi-center, non-interventional study (ChiCTR2100047990). The accrual goal is 200 patients, and the primary endpoint is overall survival (OS). Methods: We included R/R NHL patients treated with commercial Axi-cel at 20 authorized treatment centers from Nov 2021 to Nov 2023. All the patients signed written informed consent. We reported best objective response rate (bORR), best complete response (bCR) rate and adverse events of special interest (AESI), including cytokine release syndrome (CRS) and neurological events (NE). Results:Till the cut-off date of May 31, 2024, a total of 201 R/R NHL patients had undergone efficacy evaluation at month 3 (M3). The median age of patients was 56.9 (16, 82) years, with 61 patients (30.3%) aged 65 years or older. One hundred and ten (54.7%) patients were male. The baseline characteristics of these patients included 171 (85.1%) with diffuse large B-cell lymphoma, 6 (3.0%) with primary mediastinal B-cell lymphoma, and 11 (5.5%) with high-grade B-cell lymphoma, 6 (3.0%) with transformed follicular lymphoma. 50.2% of patients had an International Prognostic Index (IPI) score ≥3. The median number of prior treatment was 2. Seventy-one patients (35.3%) had received 3 line or more previous therapies and 23 patients (11.4%) had undergone autologous stem cell transplantation (ASCT). The primary refractory subgroup reached 102 (50.7%), and 81 (40.3%) patients were refractory to second-line or subsequent therapy. Notably, compared to the baseline characteristics of Axi-cel real-world studies for R/R large B-cell lymphoma (LBCL) in other countries, a greater proportion of Chinese patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) score≥2 (26.4%), HBsAg (+)(18.4%), HBsAg (-) accompanied with HBcAb (+) (33.3%). The median time from leukapheresis to infusion was 36 days. Bridging therapy was given in 128 patients (63.7%). The median follow-up was 17.6 months. The bORR and bCR rate were 83.1% and 67.2%, respectively, and M3 CR rate is 59.2%. The duration of response (DoR) rate was 65.4% at 12 months, 59.6% at 24 months. The median progression-free survival (PFS) reached 15.5 months, with PFS rates of 58.9% at 12 months, 49.8% at 24 months. The median OS was not reached and 81.6% were alive at 12 months, OS rate was 75.2% at 24 months. No new safety signals were observed in the Chinese population. CRS of any grade occurred in 172 patients (85.6%), with 21 patients (10.4%) experiencing grade≥3. NE of any grade occurred in 51 patients (25.4%), with 7 patients (3.5%) experiencing grade≥3. No grade 5 CRS or NE appeared. Patients with prior 1 line treatment were 2.2 times more likely to achieve M3 CR than those with prior≥2 lines [OR: 2.20 (95%CI, 0.98-4.91)] and a 68% lower risk of death [HR: 0.32 (95%CI, 0.11-0.95)]. Eighty-eight patients (43.8%) received combination therapy after Axi-cel infusion and before disease progression, 76.1% of them received combination therapy containing bruton's tyrosine kinase inhibitor (BTKi), multivariate analysis showed that these patients had better bORR [OR: 10.26 (95%CI, 2.66-39.65)], bCR [OR: 3.21 (95%CI, 1.37-7.48)], M3 CR [OR: 2.65 (95%CI, 1.21-5.79)], PFS [HR: 0.37 (95%CI, 0.21-0.67)], OS [HR: 0.39 (95%CI, 0.17-0.86)] than patients not received combination therapy. Conclusions: This analysis demonstrated the consistent efficacy of Axi-cel in Chinese R/R NHL patients, while NE of any grade and ≥grade 3 were lower. The early use of CAR-T therapy could yield greater benefits. BTKi may have synergy with CAR-T therapy.