Effectiveness and safety of axicabtagene ciloleucel (Axi-cel) in Chinese patients with relapsed/refractory non-Hodgkin lymphoma: Age subgroup analysis of real-world study

Abstract Background: CD19 CAR-T cells have changed the treatment landscape for relapsed/refractory non-Hodgkin lymphoma (R/R NHL) offering a potential curative-intent strategy. Axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, has demonstrated consistent efficacy in Chinese R/R NHL patients, with lower rates of neurotoxicity (NE) of any grade and ≥grade 3. Although increased risk of relapse and mortality was reported in elderly patients with R/R NHL, subgroup analysis of ZUMA-1 study showed durable response and manageable toxicity with axi-cel in R/R LBCL patients aged ≥65. Real-world data analyses from the Center for International Blood and Marrow Transplantation Research (CIBMTR) indicate that axi-cel is associated with a better prognosis compared to conventional chemoimmunotherapy in elderly patients. Here, we report a subgroup analysis comparing outcomes between patients ≥65 and <65 years of age from a Chinese real-world study (ChiCTR2100047990). Methods: Patients with R/R NHL and ≥2 lines of prior therapy were treated with commercial axi-cel at 20 Chinese centers. Axi-cel was administered at a target dose of 2×10⁶ CAR-T cells/kg. The primary endpoint was overall survival (OS). Best objective response rate (bORR), best complete response (CR) rate, and progression-free survival (PFS) were assessed. Adverse events (AEs) were graded according to NCI-CTCAE 5.0. Adverse events of special interest (AESI) included cytokine release syndrome (CRS) and neurological events (NEs). The present analysis was based on 3-month follow-up data from all patients who had completed their scheduled assessments by the data cut-off date (May 31, 2024). Results: This analysis included 160 participants stratified by age (≥65: n=51; <65: n=109), with a median follow-up of 17.6 months. Baseline characteristics, aside from age, were largely similar between patients aged ≥65 and those aged <65. Notably, the aged ≥65 subgroup demonstrated higher proportions of ECOG performance status ≥2 (37.3% vs 22.9%) and International Prognostic Index (IPI) scores 3-5 (74.5% vs 38.5%) compared with the aged <65 subgroup, consistent with the age-dependent weighting in these scoring systems. Hepatic (15.7% vs 5.5%) and renal (68.6% vs 17.4%) impairment rates were higher in the aged ≥65 subgroup. Fewer patients in aged ≥65 subgroup experienced autologous stem cell transplantation (ASCT) than those in aged <65 subgroup (39.2% vs 52.3%). Following axi-cel treatment, the aged ≥65 subgroup demonstrated a higher bORR (86.3% vs. 80.7%) and a higher CR rate (78.4% vs. 60.6%) compared to the aged <65 subgroup. The 9-month PFS rate was higher in the aged ≥65 subgroup than aged <65 subgroup (66.7% vs. 59.4%). The median overall survival (OS) was not reached. The proportion of patients who experienced grade ≥3 axi-cel-related adverse events was comparable between the two groups (92.2% vs 93.6%). Grade ≥3 NEs were infrequent in both groups and occurred at similar rates (3.9% vs. 2.7%). However, the incidence of grade ≥3 CRS was higher in the aged ≥65 subgroup (23.5% vs. 11.1%). Conclusion: In this subgroup analysis of the real-world study, axi-cel demonstrated effectiveness and tolerability in patients with R/R NHL, both in those younger than than 65 years and those aged 65 years or older. Notably, patients aged ≥65 exhibited numerically higher CR rates and improved PFS compared to younger patients (aged <65), with a manageable safety profile. These findings further support the broader use of axi-cel in older patients with R/R NHL. Clinical trial Registry: ChiCTR2100047990.