Patient-Reported Outcomes and Health-Related Quality of Life from the OUTREACH Study

Lisocabtagene maraleucel (liso-cel) is a CD19-directed 4-1BB chimeric antigen receptor (CAR) T-cell therapy that has shown clinical efficacy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Patient-reported outcome (PRO) and health-related quality-of-life (HR-QoL) results from the phase 2 OUTREACH study (NCT03744676), which enrolled patients with R/R LBCL across outpatient (OP) and inpatient (IP) settings at community sites in the United States, were presented at the 64th Annual American Society of Hematology Congress and Exposition.

Adults with R/R LBCL after ≥2 lines of therapy and Eastern Cooperative Oncology Group performance status of ≤1 were enrolled at community sites. Patients with left ventricular ejection fraction ≥40%, creatinine clearance >30 mL/min, secondary central nervous system lymphoma, and prior autologous hematopoietic stem-cell transplantation were eligible. Following leukapheresis and lymphodepleting chemotherapy, patients received liso-cel at a target dose of 100 × 10⁶ CAR T-cells. Patients completed the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) as well as the EQ-5D-5L health utility index (HUI) and visual analog scale (EQ-VAS) before treatment (≤7 days before lymphodepletion), before infusion on the day of liso-cel administration (day 1), and on days 29, 60, 90, 180, 270, 365, 545, and 730/end of study; patients also completed the questionnaires at disease progression. The primary HR-QoL domains of interest were the EORTC QLQ-C30 global health (GH)/QoL, physical functioning, role functioning, cognitive functioning, fatigue, and pain domains, as well as the EQ-5D-5L HUI and EQ-VAS. A linear mixed model for repeated measures analysis was performed to assess the least squares (LS) mean change from baseline for visits with ≥10 patients.

Among 82 liso-cel‒treated patients, completion rates for the HR-QoL assessment at baseline were high (EORTC QLQ-C30, 89%; EQ-5D-5L HUI and EQ-VAS, 93%). At baseline, patients in OUTREACH had numerically slightly worse mean scores across most domains of the HR-QoL assessment compared with the general US population with similar age and gender distributions; these differences were not statistically significant. Mean changes from baseline were maintained or improved across visits for all EORTC QLQ-C30 primary domains of interest, as well as the EQ-5D-5L HUI and EQ-VAS. Overall LS mean changes from baseline through day 730 showed significant improvements in EORTC QLQ-C30 GH/QoL (P <.001), role functioning (P = .020), fatigue (P <.001), and pain (P <.001), as well as the EQ-VAS (P <.001). Clinically meaningful improvements in fatigue and pain were observed as early as 15 and 6 weeks, respectively. At the individual level, most patients experienced either meaningful improvement or no change in the primary domains of interest, and more than half experienced meaningful improvements in GH/QoL (23%-60%), fatigue (28%-65%), and pain (39%-90%), and at most time points, with the lowest percentages observed on days 1 or 29. No significant differences in HR-QoL among patients monitored in the OP setting versus IP setting were observed.

In OUTREACH, patients had slightly impaired HR-QoL at baseline compared with the general US population. HR-QoL was either improved or maintained from baseline in most patients with R/R LBCL who received liso-cel as third-line or later treatment in OUTREACH, with the greatest improvements observed in the GH/QoL, role functioning, fatigue, and pain domains. These findings demonstrate the importance of PRO/HR-QoL assessments as supportive measurements of treatment outcomes in patients with R/R LBCL, lending support to the utilization of liso-cel in such patients at community centers and monitoring in the OP setting.

Source

Linhares Y, Liu FF, Freytes C, et al. Lisocabtagene maraleucel in patients with relapsed or refractory large B-cell lymphoma treated as outpatients or inpatients in the community/nonuniversity setting: patient-reported outcomes/health-related quality of life from the OUTREACH study. Presented at: 64th American Society of Hematology Annual Meeting and Exposition, December 10-13, 2022; New Orleans, LA. Poster presentation 4910.