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.

Figure 1.

Randomization, treatment, and follow-up of patients ≥65 years. Figure shows the disposition of patients ≥65 years randomized to axi-cel and SOC arms.

Figure 2.

Event-free survival per central review and ORR in patients ≥65 years. A, The Kaplan–Meier estimate of EFS by blinded central review in patients ≥65 years. EFS was defined as the time from randomization to the earliest date of disease progression according to the Lugano classification (17), new lymphoma therapy, death from any cause, or a best response of stable disease up to and including the response on day 150 assessment after randomization, per blinded central review. Tick marks indicate patients who did not meet the criteria for an event and were censored. B, Summary of best response by blinded central review in patients ≥65 years. ^a In the SOC arm, 1 patient had undefined disease, and 4 did not have response assessments completed. EFS, event-free survival; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 3.

OS (interim) and PFS in patients ≥65 years. A, Kaplan–Meier estimate of OS in patients ≥65 years. B, Kaplan–Meier estimate for PFS as assessed by investigator in patients ≥65 years. NR, not reached.

Figure 4.

Mixed model with repeated measures for change from baseline for prespecified patient-reported outcome endpoints in patients ≥65 years. Results were populated through month 15 due to lack of model convergence when using time points. Figures are based on Model 1. Horizontal lines, provided for clarity of interpretation, indicate the minimally important difference thresholds for clinically meaningful change. Mixed model includes variables for treatment, time, and treatment by time interaction (primary analysis) and is controlled for response to first-line therapy and age-adjusted IPI at screening. *, P < 0.05. A, The change from baseline of EORTC QLQ-C30 Physical Functioning in patients ≥65 years. B, The change from baseline of EORTC QLQ-C30 Global Health Status in patients ≥65 years. C, The change from baseline of EQ-5D-5L VAS in patients ≥65 years.