Patient-Reported Outcomes in a Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel (Axi-Cel) Versus Standard of Care Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma (ZUMA-7)

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.430-430
• Main Authors: Elsawy, Mahmoud, Chavez, Julio C., Avivi, Irit, Larouche, Jean-François, Wannesson, Luciano, Cwynarski, Kate, Osman, Keren, Davison, Kelly, Rudzki, Jakob D., Dahiya, Saurabh, Dorritie, Kathleen, Jaglowski, Samantha, Radford, John, Morschhauser, Franck, Cunningham, David, Martin Garcia-Sancho, Alejandro, Tzachanis, Dimitrios, Ulrickson, Matthew L., Karmali, Reem, Kekre, Natasha, Thieblemont, Catherine, Enblad, Gunilla, Dreger, Peter, Malladi, Ram, Joshi, Namita, Wang, Wei-Jhih, Solem, Caitlyn T., Thornton Snider, Julia, To, Christina, Kersten, Marie José
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-147598

Background: Outcomes are poor for patients with large B-cell lymphoma (LBCL) who relapse early or are refractory to first-line therapy. Furthermore, patients receiving second-line standard-of-care (SOC) therapy often report poor health-related quality of life (QoL; Lin V, et al. J Clin Oncol. 2020;38:e20070). In the ZUMA-7 (NCT03391466) pivotal Phase 3, randomized, open-label, multicenter study of axi-cel (an autologous anti-CD19 chimeric antigen receptor [CAR] T-cell therapy) versus SOC, we conducted the first comparative analysis of patient-reported outcomes (PROs) with CAR T-cell therapy versus SOC as second-line treatment in relapsed/refractory (R/R) LBCL. Methods: PRO instruments, including the EORTC QLQ-C30 (cancer-specific 30-item questionnaire including global health status, functional, and symptom scales) and the EQ-5D-5L (a general questionnaire with 5 QoL domains plus a global assessment), were administered at baseline (prior to treatment), Day 50, Day 100, Day 150, Month 9, and every 3 months from randomization up to 24 months or time of event-free survival event (disease progression, death from any cause, or new lymphoma therapy), whichever occurred first. The QoL analysis set was defined as all patients who had a baseline PRO and ≥1 measure completed at Day 50, Day 100, or Day 150. Prespecified hypotheses for 3 PRO domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QoL, and EQ-5D-5L visual analog scale [VAS]) were tested using a mixed-effect model with repeated measures at Day 100 and subsequent time points if previous time points were statistically significant. False Discovery Rate was used to adjust P values across key endpoints; sensitivity analyses were conducted to control for covariates and patterns of missingness. A clinically meaningful change was defined as 10 points for each EORTC QLQ-C30 score and 7 points for EQ-5D-5L VAS score. Exploratory analyses on other domains of EORTC QLQ-C30 and EQ-5D-5L were also performed. Results: Of 359 patients enrolled in the ZUMA-7 study, 296 patients (165 axi-cel, 131 SOC) had baseline PROs and ≥1 follow-up measure and were included for analysis. Overall, 70% of patients had primary refractory disease, 42% had high second-line age-adjusted International Prognostic Index (2-3), and 30% were ≥65 years old. For patients in the QoL analysis set treated with axi-cel versus SOC, there was a statistically significant (P