PMID- 36646322 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20240502 IS - 2666-6367 (Electronic) IS - 2666-6375 (Print) IS - 2666-6367 (Linking) VI - 29 IP - 5 DP - 2023 May TI - Quality-Adjusted Time without Symptoms or Toxicity: Analysis of Axicabtagene Ciloleucel versus Standard of Care in Patients with Relapsed/Refractory Large B Cell Lymphoma. PG - 335.e1-335.e8 LID - S2666-6367(23)00034-9 [pii] LID - 10.1016/j.jtct.2023.01.008 [doi] AB - 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. CI - Copyright (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Kersten, Marie Jose AU - Kersten MJ AD - Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands. Electronic address: m.j.kersten@amsterdamumc.nl. FAU - Qiao, Yao AU - Qiao Y AD - OPEN Health, Bethesda, Maryland. FAU - Shah, Ruchit AU - Shah R AD - OPEN Health, Bethesda, Maryland. FAU - Solem, Caitlyn AU - Solem C AD - OPEN Health, Bethesda, Maryland. FAU - Snider, Julia Thornton AU - Snider JT AD - Kite Pharma, a Gilead Company, Santa Monica, California. FAU - To, Christina AU - To C AD - Kite Pharma, a Gilead Company, Santa Monica, California. FAU - Cheng, Paul AU - Cheng P AD - Kite Pharma, a Gilead Company, Santa Monica, California. FAU - Spooner, Clare AU - Spooner C AD - Kite Pharma, a Gilead Company, Santa Monica, California. FAU - Perales, Miguel-Angel AU - Perales MA AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. LA - eng SI - ClinicalTrials.gov/NCT03391466 GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230114 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - U2I8T43Y7R (axicabtagene ciloleucel) SB - IM MH - Humans MH - Child, Preschool MH - Quality of Life MH - *Hematopoietic Stem Cell Transplantation MH - Standard of Care MH - Transplantation, Autologous MH - *Lymphoma, Large B-Cell, Diffuse/therapy MH - Disease Progression PMC - PMC10461955 MID - NIHMS1925515 OTO - NOTNLM OT - Axicabtagene ciloleucel OT - Quality of life OT - Quality-adjusted survival OT - Quality-adjusted time without symptoms or toxicity OT - Relapsed or refractory large B cell lymphoma COIS- Conflict of interest statement: There are no conflicts of interest to report. EDAT- 2023/01/17 06:00 MHDA- 2023/05/01 06:42 PMCR- 2024/05/01 CRDT- 2023/01/16 19:26 PHST- 2022/06/21 00:00 [received] PHST- 2022/09/09 00:00 [revised] PHST- 2023/01/06 00:00 [accepted] PHST- 2023/05/01 06:42 [medline] PHST- 2023/01/17 06:00 [pubmed] PHST- 2023/01/16 19:26 [entrez] PHST- 2024/05/01 00:00 [pmc-release] AID - S2666-6367(23)00034-9 [pii] AID - 10.1016/j.jtct.2023.01.008 [doi] PST - ppublish SO - Transplant Cell Ther. 2023 May;29(5):335.e1-335.e8. doi: 10.1016/j.jtct.2023.01.008. Epub 2023 Jan 14.