Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma

Abstract

Here we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy versus standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 (NCT03391466) study of axicabtagene ciloleucel (axi-cel) versus SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for QLQ-C30 Physical Functioning, Global Health Status/QoL, and EQ-5D-5L visual analogue scale (VAS) were tested using mixed-effect models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 Global Health Status/QoL (estimated difference 18.1 [95% CI, 12.3-23.9]), Physical Functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P<.0001 for all). At day 150, scores significantly favored axi-cel versus SOC for Global Health Status/QoL (9.8 [95% CI, 2.6-17.0]; P=.0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P=.0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL.

Long‐term survivorship care after CAR‐T cell therapy

“…106,[111][112][113][114] In the randomized trial ZUMA-7, second-line axi-cel was associated with a more rapid recovery of patient-reported quality of life and physical functioning by Day +100 compared to standard of care. 115 Indeed, long-term survivors of CAR-T cell therapy have overall comparable self-reported measures of mental health, fatigue, and social function as the general population. 41 Nevertheless, anxiety, depression, and other stressors continue to afflict a substantial proportion of long-term survivors, 41,106 underscoring the importance of screening and support for mental health disorders as part of routine care.…”

Data from 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

“…Prespecified hypotheses for PRO domains [EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QoL, and EQ-5D-5L visual analog scale (VAS)] were tested as previously reported (24,25). A mixed-effects model with repeated measures at day 100 and at subsequent time points conditional on statistical significance at the previous time point was used.…”

“…Safety analyses included randomized patients ≥65 years who received axicel or ≥1 dose of SOC therapy per protocol, analyzed by protocol therapy received. The QoL subgroup included patients ≥65 years who had a baseline PRO and ≥1 post-baseline measure completed (24,25).…”

CAR-T Cells in Canada; Perspective on How to Ensure We Get Our Value’s Worth

“…CAR-T cell-treated patients report dramatic changes in HRQOL related to the cumulative benefit of CAR-T cells on disease control and of the short and long-term toxicities from the cellular treatment [ 19 , 20 ]. The estimate of HRQOL can be translated into a utility score to reflect the level of physical, mental, and social functioning associated with a particular health state and be incorporated into the economic evaluation.…”

“…So far, most studies have demonstrated improvement in HRQOL with CAR-T cell treatment in patients with r/r DLBCL, but the results published so far lack validity for patients who receive publicly funded CAR-T therapy in Canada, since only patients with aggressive B-cell lymphoma who are either primary refractory or who have relapsed after two lines of therapy are eligible for CAR-T reimbursement. [ 19 , 21 , 22 , 23 , 24 , 25 ].…”