SAFETY AND EFFICACY OF AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN OLDER PATIENTS: RESULTS FROM THE US LYMPHOMA CAR‐T CONSORTIUM (2019)

†DS and LL contributed equally. Introduction: Axi-cel, an autologous anti-CD19 CAR T-cell therapy, induced an overall response rate (ORR) of 83% and complete response (CR) rate of 58% in patients with refractory large B-cell lymphoma on the pivotal ZUMA-1 study. At a median follow-up of 27.1 mo, 39% of the patients remain in remission (Neelapu et al. N Eng J Med 2017; Locke et al, Lancet Oncol 2019). Here, we present retrospective analysis of safety and efficacy outcomes in older patients treated with axi-cel in the post-approval setting from a 17-center US Lymphoma CAR-T Consortium. Methods: Patients with relapsed/refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high-grade B-cell lymphoma, or transformed follicular lymphoma, received axi-cel infusion following conditioning with cyclophosphamide and fludarabine. Bridging therapy was allowed. Cytokine release syndrome (CRS) was graded by Lee criteria and neurotoxicity (CAR-related encephalopathy syndrome or CRES) was graded according to CTCAE or CARTOX system. Results: Of 300 apheresed patients, 206 (69%) were <65 years (yrs) and 94 (31%) were ≥65 yrs. Baseline characteristics such as gender, ECOG performance status, stage, number of prior lines of therapy, prior autologous transplant, refractory status, and bridging therapy usage were comparable between the two groups but patients ≥65 yrs had higher IPI (IPI 3-5: 77% vs. 44%, P<0.001). Of the apheresed patients, 14 (7%) patients <65 yrs and 10 (11%) patients ≥65 yrs did not receive axi-cel. Overall, 274 patients (191 <65 vs. 83 ≥65) were evaluable for safety and 272 patients (190 <65 vs. 82 ≥65) were evaluable for efficacy. Of the axi-cel-treated patients, best ORR through day 90 was comparable between the two groups (82% for all patients; 82% <65 vs. 84% ≥65, P = 0.61) but CR rate was higher in patients ≥65 yrs (57% for all patients; 51% <65 vs. 71% ≥65, P<0.01). Median follow-up for all patients was 5.9 months. Estimated median PFS (7.4 mo <65 vs. 9.2 mo ≥65, P = 0.83) and OS (18.7 mo <65 vs. not assessable ≥65, P = 0.99) were comparable between the two groups. Incidence and severity of CRS was comparable in both groups (all CRS grades: 91% <65 vs. 92% ≥65; grade ≥3 CRS: 7% in both groups). There was a trend towards higher incidence of CRES in older patients (all CRES grades: 65% <65 vs. 78% ≥65, P = 0.08) but grade ≥3 CRES was comparable (31% <65 vs. 35% ≥65, P = 0.53). There were two axi-cel-related deaths, one in each group. The use of tocilizumab and corticosteroids were not significantly different between the two groups. Median hospitalization period was 14 days in both groups and ICU admission rate was 32% in both groups. These safety and efficacy results had similar pattern when patients were grouped based on age cut-off of 60 or 70 yrs. Conclusions: Our results suggest that the safety and efficacy of axi-cel are largely comparable between younger and older patients with the exception of CR rate, which was higher in older patients. Keywords: CD19; diffuse large B-cell lymphoma (DLBCL); elderly.