S211: CLINICAL AND PATIENT-REPORTED OUTCOMES IN A PHASE 3 STUDY OF AXICABTAGENE CILOLEUCEL (AXI-CEL) VS STANDARD-OF-CARE IN ELDERLY PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (ZUMA-7)

Background: The median age at large B-cell lymphoma (LBCL) diagnosis is 66 years, and older patients with relapsed/refractory (R/R) LBCL are at risk of inferior outcomes, increased toxicity, and inability to tolerate second-line standard-of-care (SOC) treatment (Di M, et al. Oncologist. 2021). Further, second-line SOC treatment is often associated with poor health-related quality of life (Lin V, et al. J Clin Oncol. 2020;38:e20070). In the global Phase 3, randomized ZUMA-7 study, axi-cel, an autologous anti-CD19 CAR T-cell therapy, significantly improved event-free survival (EFS; hazard ratio [HR], 0.398, P<0.0001; median 8.3 vs 2 months, respectively) compared with second-line SOC in R/R LBCL (Locke FL, et al. N Engl J Med. 2022;386:640-654). Aims: Here we report results of a planned subgroup analysis of the ZUMA-7 study assessing outcomes, including patient-reported outcomes (PROs), of second-line axi-cel vs SOC in patients aged ≥65 years. Methods: Patients with ECOG performance status 0-1 and R/R LBCL ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axi-cel or SOC (2-3 cycles of platinum-based chemoimmunotherapy; patients with partial or complete response [CR] proceeded to high-dose therapy with autologous stem cell transplantation). PRO instruments, including the EORTC QLQ-C30 (Global Health and Physical Functioning) and the EQ-5D-5L visual analog scale (VAS), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, and Month 9, then every 3 months up to 24 months or time of EFS event, whichever occurred first. The quality-of-life analysis set included all patients who had a baseline PRO and ≥1 completed measure at Day 50, 100, or 150. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. Results: The data cutoff for this analysis was March 18, 2021 and included 51 axi-cel and 58 SOC patients with median ages of 70 years (range, 65-80) and 69 years (range, 65-81), respectively. At baseline, more axi-cel vs SOC patients had high-risk features, including second-line age-adjusted International Prognostic Index 2-3 (53% vs 31%) and elevated lactate dehydrogenase (61% vs 41%). EFS was superior with axi-cel vs SOC (HR, 0.276, P<0.0001), with higher CR rates (75% vs 33%). Grade ≥3 treatment-emergent adverse events (AEs) occurred in 94% and 82% of axi-cel and SOC patients, respectively, and Grade 5 treatment-related AEs occurred in 0 and 1 patient. In the quality-of-life analysis set comprising 46 axi-cel and 42 SOC patients, there were statistically significant and clinically meaningful differences in mean change of scores from baseline at Day 100 favoring axi-cel for EORTC QLQ-C30 Global Health (P<0.0001) and Physical Functioning (P=0.0019) and EQ-5D-5L VAS (P<0.0001). For all 3 domains, scores also favored (P<0.05) axi-cel over SOC at Day 150. The mean estimated scores numerically returned to or exceeded baseline scores earlier in the axi-cel arm (by Day 150) but never equaled or exceeded baseline scores by Month 15 in the SOC arm. Summary/Conclusion: Axi-cel demonstrated superiority over second-line SOC in patients ≥65 years with significantly improved EFS and a manageable safety profile. Axi-cel also showed meaningful improvement in quality of life over SOC, measured by multiple validated PRO instruments, with suggested faster recovery to pretreatment quality of life. The superior clinical outcomes and patient experience with axi-cel over SOC should help inform treatment choices in second-line R/R LBCL for patients ≥65 years.

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