Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma

Abstract

Purpose: Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients ≥65 years in ZUMA-7. Patients and Methods: Patients with LBCL refractory to or relapsed ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel [axi-cel; autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy] or standard of care (SOC; 2–3 cycles of chemoimmunotherapy followed by HDT-ASCT). The primary endpoint was event-free survival (EFS). Secondary endpoints included safety and patient-reported outcomes (PROs). Results: Fifty-one and 58 patients aged ≥65 years were randomized to axi-cel and SOC, respectively. Median EFS was greater with axi-cel versus SOC (21.5 vs. 2.5 months; median follow-up: 24.3 months; HR, 0.276; descriptive P < 0.0001). Objective response rate was higher with axi-cel versus SOC (88% vs. 52%; OR, 8.81; descriptive P < 0.0001; complete response rate: 75% vs. 33%). Grade ≥3 adverse events occurred in 94% of axi-cel and 82% of SOC patients. No grade 5 cytokine release syndrome or neurologic events occurred. In the quality-of-life analysis, the mean change in PRO scores from baseline at days 100 and 150 favored axi-cel for EORTC QLQ-C30 Global Health, Physical Functioning, and EQ-5D-5L visual analog scale (descriptive P < 0.05). CAR T-cell expansion and baseline serum inflammatory profile were comparable in patients ≥65 and <65 years. Conclusions: Axi-cel is an effective second-line curative-intent therapy with a manageable safety profile and improved PROs for patients ≥65 years with R/R LBCL.

Car-T Cell Therapy in Large B Cell Lymphoma

“…[8][9] A subgroup analysis of the ZUMA-7 study limited to patients 65 years of age or older showed a higher rate of ORR and CRR in the Axi-Cel group compared to the standard care group (ORR 88% vs 52%, respectively; CRR 75% vs 33%, respectively). 10 In particular, no grade 5 cytokine release syndrome or neurologic events occurred in this group of patients who are more fragile and at risk for complications. 10 The ZUMA-7 trial was preceded by the ZUMA-1 trial exploring the efficacy of Axi-Cel in third-line therapy.…”

“…10 In particular, no grade 5 cytokine release syndrome or neurologic events occurred in this group of patients who are more fragile and at risk for complications. 10 The ZUMA-7 trial was preceded by the ZUMA-1 trial exploring the efficacy of Axi-Cel in third-line therapy. ZUMA-1 was a single-arm phase I/II study enrolling LBCL patients with refractory or relapsed disease after autologous stem cell transplantation; the patients received a target dose of 2x10 6 CAR-T cells per Kg of body weight after conditioning chemotherapy with fludarabine and cyclophosphamide.…”

Current development of chimeric antigen receptor T‐cell therapy for diffuse large B‐cell lymphoma and high‐grade B‐cell lymphoma

“…Other than biological risk factors, patients with advanced age (>65 years) and comorbidities who may not be suitable for autoSCT could be reasonable candidates for second‐line CAR T‐cell therapy (all three trials included ~30% of the patients in this age group). In the post hoc analysis of ZUMA‐7 which included elderly patients (age ≥ 65), median EFS was greater with axi‐cel than with SOC (21.5 months vs. 5 months; HR, 0.276; p < .0001) 25 . The PILOT study investigated the utility of liso‐cel as a second‐line treatment for patients with r/r DLBCL not intended for autoSCT 26 .…”

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma

“…CAR NK cells will release perforin and granzymes to kill tumor cells (c). Most CAR-T therapies consist of autologous T cells, whereas CAR-NK cell therapies can be generated from allogeneic donors with R/R DLBCL [69].…”