Abstract
ZUMA-7 (NCT03391466) and ALYCANTE (NCT04531046) evaluated axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell (CART) therapy, as second-line (2L) therapy in patients with high-risk relapsed/refractory large B-cell lymphoma (R/R LBCL), with ZUMA-7 patients being autologous stem-cell transplant (ASCT) eligible whereas ALYCANTE patients were ASCT ineligible. With CAR T now established as 2L standard of care, this analysis assessed efficacy, safety and HRQoL across the full CAR T–eligible population to explore whether ASCT eligibility impacts axi-cel outcomes.
Data from axi-cel patients in ZUMA-7 and ALYCANTE were pooled without weighting. Efficacy endpoints evaluated in this analysis were event-free survival (EFS), overall response rate (complete + partial metabolic response [CMR + PMR]) and CMR, defined from leukapheresis; overall survival (OS) and progression-free survival (PFS), defined from axi-cel infusion; and duration of response (DOR). EFS and other time-to-event (TTE) outcomes were analyzed using Kaplan-Meier methods with aligned and pre-specified definitions and censoring rules. CMR and ORR were summarized with response rates. Safety was evaluated based on treatment-emergent adverse events (TEAEs) occurring after axi-cel infusion. Both trials included patient-reported outcomes using EQ-5D-5L and EORTC QLQ-C30. Longitudinal HRQoL outcomes were assessed using mixed models for repeated measures.
ZUMA-7 had a 4-year follow-up post-randomization, whereas ALYCANTE had a 2-year follow-up post-infusion. Compared to ALYCANTE, patients in ZUMA-7 were younger (mean age: 58 vs. 70 years), less frequently male (61.1% vs. 73.9%), had better performance status at screening (ECOG 0: 52.8% vs. 43.5%) and were less likely to have relapsed (26.1% vs. 44.9%) or previously had an ORR (58.9% vs. 75.9%). Race and ethnicity data were not collected in ALYCANTE, preventing comparison on these variables.
Efficacy analyses included 178 and 69 leukapheresed patients from ZUMA-7 and ALYCANTE, respectively. For all TTE outcomes, trends were very similar between the two trials. After 24 months, ZUMA-7 had 45.4% EFS, 62.8% OS and 47.6% PFS, while ALYCANTE had 44.7% EFS, 70.8% OS and 46.8% PFS, leading to pooled results of 45.2% EFS, 64.9% OS and 47.4% PFS. Pooled 12-month DOR was 61.0% (ZUMA-7 60.6%, ALYCANTE 62.1%). Pooled CMR was 55.6% at 3 months (ZUMA-7 51.2%, ALYCANTE 67.7%), while pooled ORR at 12 months was 46.6% (ZUMA-7 46.5%, ALYCANTE 46.8%).
The safety analysis included 170 (ZUMA-7) and 62 (ALYCANTE) axi-cel infused patients, with similar patterns between the trials. The incidence of grade ≥ 3 TEAEs was similar between ZUMA-7 and ALYCANTE populations, 91.2% and 88.7% respectively, with a pooled incidence of 90.5%. Grade ≥ 3 anemia TEAEs occurred in 30.0% of ZUMA-7 patients and 21.0% of ALYCANTE patients, with a pooled incidence of 27.6%. Pooled incidence of grade ≥ 3 neurologic events and neutropenias were 19.8% (ZUMA-7 21.2%, ALYCANTE 16.1%) and 64.7% (ZUMA-7 70.0%, ALYCANTE 50.0%), respectively. Non-relapse mortality was attributed to adverse events in 5.6% (ZUMA-7 4.7%, ALYCANTE 8.1%), secondary malignancies in 0.9% (ZUMA-7 1.2%, ALYCANTE 0%), and other causes in 6.5% (ZUMA-7 7.7%, ALYCANTE 3.2%) of patients.
HRQoL patterns were broadly consistent across both trials. In ALYCANTE, a clinically meaningful improvement in EQ-5D-5L VAS scores was observed at Day 100 (+9.9), while in ZUMA-7, VAS scores demonstrated a more gradual improvement, reaching clinical significance at Month 12 (+9.9). For EORTC QLQ-C30 global health status, both trials showed a transient decline at Day 50 (ZUMA-7 -7.2, ALYCANTE -6.3), followed by recovery and improvement by Month 24. This improvement was clinically meaningful in ALYCANTE (+10.6), but did not reach the threshold in ZUMA-7 (+9.6). Physical function also declined transiently in both trials at Day 50 (-12.9 for both), with ZUMA-7 showing statistically significant improvement from baseline by Month 24 (+4.1), while ALYCANTE showed a smaller, non-significant gain (+2.4).
Efficacy, safety, and HRQoL patterns were consistent across both ZUMA-7 and ALYCANTE populations. These data support the use of axi-cel regardless of transplant eligibility and reinforce the transition from ASCT to CAR T eligibility in 2L therapy.
