P1710: LISOCABTAGENE MARALEUCEL (LISO-CEL) AS SECOND-LINE TREATMENT FOR R/R LARGE B-CELL LYMPHOMA (LBCL) IN PATIENTS NOT INTENDED FOR HSCT: PATIENT-REPORTED OUTCOMES (PRO) FROM THE PHASE 2 PILOT STUDY

Abstract

Background: The PILOT study (NCT03483103) evaluated liso-cel, an autologous, CD19-directed, chimeric antigen receptor T cell product, as second-line treatment in patients with relapsed or refractory (R/R) LBCL not intended for hematopoietic stem cell transplantation (HSCT). Aims: To analyze changes in health-related quality of life (QOL) with respect to functioning and symptoms in PILOT. Methods: Adults with R/R LBCL after first-line treatment were eligible. Patients were deemed not candidates for high-dose chemotherapy and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperative Oncology Group performance status of 2, diffusing capacity for carbon monoxide ≤ 60%, left ventricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items (EORTC QLQ-C30), Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS), and EQ-5D-5L health utility index (HUI) and visual analog scale (VAS) questionnaires at screening (baseline), pretreatment (within 7 days before lymphodepletion), preinfusion on the day of liso-cel infusion (Day 1), posttreatment on Days 29, 60, 90, 180, 270, 365, 545, and 730/end of study after lisocel infusion, or after disease progression. The PRO-evaluable set included all liso-cel treated patients with baseline and ≥ 1 postbaseline assessments. Linear mixed-effects models for repeated measures assessed the least squares (LS) mean change from baseline for visits with ≥ 10 patients. Meaningful change from baseline was calculated using responder definitions of 10 points for EORTC QLQ-C30, 3 points for FACT-LymS, 0.08 points for EQ-5D-5L HUI, and 7 points for EQ-VAS. Results: Among the PRO-evaluable set (EORTC QLQ-C30, n = 56; FACT-LymS, n = 49; EQ-5D-5L HUI, n = 55; EQ-VAS, n = 54), completion rates were high (≥ 80%) across most visits for all measures. For the EORTC QLQ-C30, mean baseline fatigue was meaningfully worse than in a general population (difference of > 10 points). Overall LS mean changes through Day 545 showed significant improvements in EORTC QLQ-C30 fatigue, pain, and appetite loss, FACT-LymS, and EQ-VAS (Table). Improvement for FACT-LymS was also clinically meaningful. Fatigue improvement was clinically meaningful with a more sensitive minimal important difference of 4 (Cocks et al, 2012). Significant worsening was not observed for any domain. In patient-level analyses, a majority of patients remained stable or achieved clinically meaningful improvement at Month 6 in EORTC QLQ-C30 global health status/QOL (93% of patients), physical functioning (80%), role functioning (90%), cognitive functioning (83%), fatigue (87%), pain (80%), FACT-LymS (96%), EQ-5D-5L HUI (86%), and EQ-VAS (93%). Further, 70% and 60% of patients achieved meaningful improvements in FACT-LymS and EORTC QLQ-C30 fatigue, respectively. Image:Summary/Conclusion: Liso-cel meaningfully improved fatigue and FACT-LymS scores without negatively impacting other QOL measures. These data support the clinical evidence of liso-cel as a potential new second-line treatment in patients with R/R LBCL not intended for HSCT.