Lisocabtagene maraleucel for second-line relapsed or refractory large B-cell lymphoma: patient-reported outcomes from the PILOT study

Abstract

In the single-arm, open-label, multicenter, phase II PILOT study, second-line treatment with the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) for whom hematopoietic stem cell transplantation (HSCT) was not intended resulted in high response rates, durable responses, and a safety profile consistent with previous reports. Here, we analyzed changes in health-related quality of life (HRQOL) in patients who received liso-cel in PILOT. Patients received liso-cel, an autologous, CD19-directed, 4-1BB CAR T-cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, for a total target dose of 100×10⁶ CAR+ T cells. HRQOL, a secondary endpoint of PILOT, was assessed as prespecified using three patient-reported outcome instruments (EORTC QLQ-C30; FACT-LymS; EQ-5D-5L). Evaluable datasets for the EORTC QLQ-C30, FACT-LymS, and EQ-5D-5L health utility index, and visual analog scale (EQ-VAS) included 56 (92%), 49 (80%), 55 (90%), and 54 (89%) patients, respectively. Clinically meaningful improvement was achieved across most post-treatment visits for EORTC QLQ-C30 fatigue and FACT-LymS. Overall mean changes from baseline through day 545 showed significant improvements in EORTC QLQ-C30 fatigue, pain, and appetite loss, FACT-LymS, and EQ VAS. In within-patient analyses, clinically meaningful improvements or maintenance in scores were observed in most patients at days 90, 180, 270, and 365. HRQOL was maintained or improved in patients who received liso-cel as second-line therapy in PILOT. These findings support liso-cel as a preferred second-line treatment in patients with R/R LBCL not intended for HSCT (clinicaltrials gov. Identifier: NCT03483103).

Figure 1.

Least squares mean changes from baseline in the primary domains of interest over time. For the EORTC QLQ-C30 domains of GH/QOL (A), physical functioning (B), role functioning (C), cognitive functioning (D), fatigue (E), and pain (F), 2 sets of minimally important differences (MID) were used to assess whether a change from baseline (BL) (improvement or deterioration) was clinically meaningful: the conventional 10-point change suggested by Osoba et al. (dotted gray lines) and the MID suggested by Cocks et al. (dashed red lines). For the FACT-LymS (G), an MID of 3 points, as suggested by Hlubocky et al. (dotted dark blue lines),^, was used to identify clinically meaningful improvement and deterioration from BL. For the EORTC QLQ-C30 GH/QOL and functioning domains, an increased score indicates improved QOL/functioning; for the EORTC QLQ-C30 symptom domains, an increased score indicates worsening symptoms. For FACT-LymS, an increased score indicates improved QOL. LS: least squares; CI: confidence interval; EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items; GH: global health; QOL: quality of life; FACT-LymS: Functional Assessment of Cancer Therapy - Lymphoma “Additional Concerns” Subscale.

Figure 2.

Within-patient analysis of changes from baseline for the primary domains of interest. Responder definitions of 10 for the EORTC QLQ-C30 domains of GH/QOL (A), physical functioning (B), role functioning (C), cognitive functioning (D), fatigue (E), and pain (F) and 3 for FACT-LymS (G), were applied. Data are shown up to the last visit with ≥10 patients. Gold bars indicate improvement, light blue bars indicate no change, and aqua bars indicate worsening from baseline. EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items; GH: global health; QOL: quality of life; FACT-LymS: Functional Assessment of Cancer Therapy - Lymphoma “Additional Concerns” Subscale.