Lisocabtagene Maraleucel (Liso-cel) in Patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) Treated As Outpatients or Inpatients in the Community/Nonuniversity Setting: Patient-Reported Outcomes/Health-Related Quality of Life from the Outreach Study

Background: Liso-cel is an autologous, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8⁺ and CD4⁺ CAR⁺ T cells that has shown clinical efficacy in patients with R/R LBCL. In TRANSCEND NHL 001 (NCT02631044), patients with third-line or later LBCL treated with liso-cel at academic centers had early, sustained, and clinically meaningful improvements in health-related quality of life (HRQOL) and symptoms that correlated with antitumor activity (Patrick et al. Blood Adv 2021). Here we present patient-reported outcome (PRO)/HRQOL results from the OUTREACH study (NCT03744676), which enrolled patients with R/R LBCL across outpatient and inpatient settings at community sites in the United States. We aimed to assess whether HRQOL among patients treated with liso-cel would, at a minimum, be maintained over the course of the study.

Methods: Adults with R/R PET-positive LBCL after ≥ 2 lines of therapy and ECOG PS ≤ 1 were enrolled at community (nontertiary care) sites. Patients with mild to moderate organ function (LVEF ≥ 40%; serum CrCl > 30 mL/min), secondary CNS lymphoma, and prior autologous HSCT were eligible. After leukapheresis and lymphodepleting chemotherapy, patients received liso-cel at a target dose of 100 × 10⁶ CAR⁺ T cells. Patients completed European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) and EQ-5D-5L (health utility index [HUI] and visual analog scale [VAS]) before treatment (≤ 7 days before lymphodepletion; baseline); before infusion on day of liso-cel infusion (Day 1); and on Days 29, 60, 90, 180, 270, 365, 545, and 730/end of study; and at disease progression. The primary HRQOL domains of interest were the EORTC QLQ-C30 global health status/QOL, physical functioning, role functioning, cognitive functioning, fatigue, and pain. 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. Within-patient meaningful change from baseline was calculated using responder definitions (in points): 5-30 for EORTC QLQ-C30 (based on thresholds set by Cocks and Buchanan [ISOQOL 2015]), 0.08 for EQ-5D-5L HUI, and 7 for EQ-5D-5L VAS. Within-group meaningful change from baseline was defined by the minimally important differences set by Cocks et al (Eur J Cancer 2012).

Results: Among the 79 liso-cel‒treated patients, completion rates for the HRQOL assessment were high (≥ 70%) across most visits for all measures. For EORTC QLQ-C30, mean baseline scores were meaningfully worse than in a general noncancer population (difference of ≥ 10 points) for role functioning and fatigue. The overall LS mean change from baseline showed significant and meaningful improvement for the primary domains of EORTC QLQ-C30 global health status/QOL, fatigue, and pain, as well as the EQ-5D-5L VAS (Table). Cognitive functioning and HUI were comparable with the general population at baseline and were maintained over time after liso-cel infusion. In individual assessments across visits, most patients (57%‒100%) experienced either meaningful improvement or no meaningful improvement or deterioration for all domains, and more than half achieved meaningful improvement in global health status/QOL (32.9%‒59.5%), fatigue (27.1%‒65.5%), pain (38.6%‒66.7%), and EQ-5D-5L VAS (27.8%‒71.4%) at most time points, with lowest percentages observed on Day 1. Results comparing PRO/HRQOL data for patients treated in an outpatient versus inpatient setting will be reported in the presentation.

Conclusions: In the OUTREACH study, patients had impaired HRQOL at baseline compared with the general noncancer population. HRQOL 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 Global health status/QOL, fatigue, and pain domains. These findings show the importance of PRO/HRQOL assessments as supportive measurements of treatment outcome in patients with R/R LBCL, and they lend support to the use of liso-cel in treating patients with R/R LBCL at community centers and in the outpatient setting.

Linhares:glaxosmithkline: Other: advisory board; ADC therapeutics: Other: advisory board, Research Funding; Gilead Sciences, Inc.: Other: advisory board; BeiGene USA, Inc.: Other: advisory board, Research Funding; Seagen Inc: Other: advisory board, Research Funding; Bristol Myers Squibb: Other: advisory board, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Other: advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Other: advisory board; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Curio Science: Other: Workshop Participation and Moderation. Liu:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Cherry:BMS: Other: Ad Board. Shi:Evidera: Current Employment, Other: Current Employee at Evidera which received research funding from Bristol Myers Squibb. Liao:Evidera: Current Employment, Other: Current Employee at Evidera which received research funding from Bristol Myers Squibb. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Espinola:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Vedal:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Mattar:Gilead: Speakers Bureau; Takeda: Speakers Bureau.