The quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology provides a comprehensive framework for treatment comparison that partitions survival time into distinct health states reflecting both treatment toxicity and disease progression. ZUMA-7 (ClinicalTrials.gov identifier NCT03391466), a phase 3 randomized open-label multicenter study, was conducted to evaluate the efficacy of axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T cell therapy, compared with standard of care (SOC) involving platinum-based salvage chemotherapy with autologous stem cell transplantation (ASCT) consolidation as a second-line treatment for relapsed/refractory (R/R) large B cell lymphoma (LBCL), and met its primary endpoint of improved event-free survival (EFS). We aimed to use the Q-TWiST method to compare the quality-adjusted survival of R/R LBCL patients treated with axi-cel and those treated with SOC who were enrolled in ZUMA-7. The preplanned analysis of overall survival (OS) was partitioned into 3 mutually exclusive health states: time with grade ≥3 adverse events before the event as defined in the EFS analysis (TOX), time without severe toxicity before the event (TWiST), and time after the event (REL). Q-TWiST was computed as a weighted sum of mean TOX, TWiST, and REL values multiplied by state-specific quality of life (QoL) utility scores. Q-TWiST was evaluated in the intention-to-treat cohort at median follow-up. A relative Q-TWiST gain of 10% was deemed "clinically important" and a gain of ≥15% was deemed "clearly clinically important" based on established categorization. Sensitivity analyses with follow-up ranging from 3 months to the maximum follow-up and subgroup analyses by age and R/R status were explored. At a median follow-up of 23.5 months, the axi-cel cohort showed a significantly longer time without severe toxicity compared with the SOC cohort, with a mean TWiST duration of 11.18 months versus 5.39 months, respectively. The mean TOX was 1.16 months versus .74 months, and mean REL was 6.02 months versus 10.66 months. Quality-adjusted survival was significantly longer with axi-cel by 3.7 months (95% CI, 2.3 to 5.2 months), representing a relative gain of 21.9%. This was reflected across all subgroups, with estimated Q-TWiST gains of 3.1 months (95% CI, 1.5 to 4.9 months) for patients age <65 years, 5.2 months (95% CI, 2.4 to 7.9 months) for those age ≥65 years, 3.2 months (95% CI, 1.4 to 4.9 months) for those with primary refractory disease, 9.1 months (95% CI, 3.9 to months 13.5) for those who relapsed within 6 months, and 4.1 months (95% CI, 1.1 to 7.1 months) for those who relapsed between 6 and 12 months. The Q-TWiST gain for axi-cel also was statistically significant across follow-up durations, increasing from .2 month (95% CI, .1 to .3 month) at a 3-month follow-up to 4.9 months (95% CI, 2.4 to 7.8 months) at the maximum follow-up of 37.7 months. Axi-cel was associated with a statistically significant and "clearly clinically important" gain in quality-adjusted survival, regardless of the relative decline in QoL associated with treatment toxicity, disease progression, or additional cancer treatment. This finding adds to the existing evidence supporting a benefit for axi-cel as a second-line treatment for patients with R/R LBCL.