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

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 = 65 years were random-ized 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 = 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 = 65 and = 65 years with R/R LBCL

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.

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 \u3c 0.0001). Objective response rate was higher with axi-cel versus SOC (88% vs. 52%; OR, 8.81; descriptive P \u3c 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 \u3c 0.05). CAR T-cell expansion and baseline serum inflammatory profile were comparable in patients ≥65 and 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

Supplementary Figure S2 from 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

Overall survival (interim) and progression-free survival in patients ≥70 years</p

Supplementary Figure S3 from 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

Sensitivity analysis of interim overall survival in patients ≥65 years</p

Supplementary Figure S1 from 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

Event-free survival per central review and objective response rate in patients ≥70 years</p

Supplementary Figure S4 from 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

Mixed model with repeated measures for change from baseline for prespecified patient-reported outcomes endpoints in patients ≥65 years</p

Supplementary Tables S1-S11 from 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

Tabulated data supporting ZUMA-7 elderly analysis Supplementary Table S1. Patient-reported outcomes instruments Supplementary Table S2. Axi-cel delivery and administration time Supplementary Table S3. Summary of efficacy and safety outcomes in patients ≥65 years versus all patients in ZUMA-7 Supplementary Table S4. Serious adverse events in at least 3 patients in patients ≥65 years Supplementary Table S5. Summary of cytopenias present on or after 90 days from initiation of definitive therapy on protocol in patients ≥65 years Supplementary Table S6. Deaths in axi-cel and SOC arms for patients ≥65 years (safety analysis set) Supplementary Table S7. Summary of serum analytes in patients <65 years versus ≥65 years in the axi-cel arm (N = 170) Supplementary Table S8. Most common adverse events, cytokine release syndrome, and neurologic events in patients ≥70 years Supplementary Table S9. Deaths in axi-cel and SOC arms for patients ≥70 years Supplementary Table S10. Baseline characteristics for quality-of-life analysis in patients ≥65 years Supplementary Table S11. Mixed model with repeated measures estimated difference in change from baseline for prespecified patient-reported outcomes measures (quality-of-life analysis set) in patients ≥65 years</p

Supplementary Figure S5 from 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

CAR T-cell levels in patients ≥65 years</p