2021 - Health-related quality of life in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with liso-cel in TRANSCEND CLL 004

Introduction: Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), especially those with progression on Bruton tyrosine kinase inhibitors (BTKi) and venetoclax failure, have limited treatment options and poor patient-reported outcomes (PRO)/health-related quality of life (HRQOL). The CD19-directed chimeric antigen receptor T cell therapy lisocabtagene maraleucel (liso-cel) is being evaluated in R/R CLL/SLL in the phase 1/2 TRANSCEND CLL 004 study (NCT03331198). Here, we report PRO/HRQOL for patients in the phase 2 part of TRANSCEND CLL 004.

Methods: Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-30 items (C30), EORTC QLQ-17 items for CLL (CLL17), and EQ-5D-5L at baseline (≤ 7 days before lymphodepletion), preinfusion on the day of liso-cel infusion (Day 1), and 30, 60, 90, 180, 270, 365, 455, 545, and 730 days after infusion. The primary domains of interest were EORTC QLQ-C30 global health status (GHS)/quality of life (QOL), physical functioning, role functioning, cognitive functioning, and fatigue and EORTC QLQ-CLL17 symptom burden and physical condition/fatigue. The PRO-evaluable population was defined as patients with baseline and ≥ 1 postbaseline PRO assessment, among all patients who received leukapheresis in the phase 2 portion. Observed scores and mean changes from baseline were calculated across postbaseline visits. Intra-patient meaningful changes from baseline were calculated using prespecified change thresholds.

Results: Of 112 patients in the PRO-evaluable population and 70 in the BTKi progressed/venetoclax failure subset, baseline completion rates were 61% in both populations, with rates of 40%‒70% across most visits for all measures. The main reasons for not completing PROs were COVID-19‒related restrictions. Outcomes were similar in both populations. Mean baseline scores were worse than those of the United States general population for many domains. After initial deterioration in HRQOL after liso-cel infusion, the observed mean changes from baseline showed improvement starting at Day 60 for all primary domains (representative domains shown in Figure) except for cognitive functioning score, which was comparable with the general population at baseline and maintained over time. The proportion of patients with meaningful improvement increased over time for multiple domains, including fatigue-related domains and GHS/QOL on the EORTC QLQ-C30 and EORTC QLQ-CLL17. From Day 90 through Day 730, the proportions of patients with meaningful improvement or no change on the primary domains exceeded the proportion with meaningful deterioration.

Conclusions: Liso-cel either improved or maintained HRQOL from baseline in patients with heavily pretreated R/R CLL/SLL. Meaningful improvements were achieved in the key CLL symptom of fatigue and overall QOL.