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 (pt) 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 pt-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 pts in the phase 2 part of TRANSCEND CLL 004. Methods: Pts 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 pts with baseline and ≥1 postbaseline PRO assessment, among all leukapheresed pts in the phase 2 portion. Observed scores and mean changes from baseline were calculated across postbaseline visits. Intra-pt meaningful changes from baseline were calculated using prespecified change thresholds. Results: Of 112 pts 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 pts 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 pts with meaningful improvement or no change on the primary domains exceeded the proportion with meaningful deterioration. The research was funded by: This study was funded by Juno Therapeutics, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Stephen Gilliver, PhD, of Evidera (Bethesda, MD, USA), and Bu Reinen, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb. Keyword: Cellular therapies Conflicts of interests pertinent to the abstract. D. G. Maloney Consultant or advisory role: A2 Biotherapeutics, Member of the Scientific Advisory Board, Navan Technologies, Member of the Scientific Advisory Board, Chimeric Therapeutics, Member of the Scientific Advisory Board, Genentech, Member and Chair of the Lymphoma Steering Committee, BMS, Member of the JCAR017 EAP-001 Safety Review Committee, BMS, Member, CLL Strategic Council, ImmPACT Bio, Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program, Gilead Sciences, Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies, Interius. Member, Clinical Advisory Board, BMS, Member of the JCAR017-BCM-03 Scientific Steering Committee Stock ownership: A2 Biotherapeutics, Navan Technologies Honoraria: BMS, Caribou Biosciences, Inc., Celgene, Genentech, Incyte, Juno Therapeutics, Kite, Lilly, Mustang Bio, Novartis, Umoja Research funding: Kite Pharma, Juno Therapeutics, Celgene, Legend Biotech, BMS Other remuneration: Rights to royalties from Fred Hutch for patents licensed to Juno Therapeutics/BMS T. Siddiqi Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics Other remuneration: Speaker's Bureau: Astra Zeneca, BMS, Beigene B. Fakhri Consultant or advisory role: Abbvie, BMS, Beigene, Astrazeneca, Adaptive, pharmacyclics, CSL Behring, LOXO-Lilly Research funding: Abbvie, BMS, Angiocrine, Loxo-Lilly Educational grants: Abbvie S. Ma Consultant or advisory role: Abbvie, AstraZeneca, Beigene, BMS, Genentech, Janssen, TG Therapeutics Honoraria: Abbvie, AstraZeneca, Beigene, BMS, CCO, Curio Science, Dava Oncology, Genentech, Janssen, Lilly, Medscape, OncLive, TG Therapeutics Research funding: Abbvie, AstraZeneca, Beigene, Juno, Loxo Oncology, TG Therapeutics Other remuneration: Speaker's Bureau: AstraZeneca, Beigene, Janssen, Lilly, Pharmacyclics N. N. Shah Consultant or advisory role: Kite/Gilead, Loxo/Lilly, TG Therapeutics, Seattle Genetics, Incyte, Novartis, Juno/BMS, Janssen, Miltenyi Biotec Stock ownership: Tundra Therapeutics Research funding: Miltenyi Biotec, Loxo/Lilly, Adaptive Biotechnologies P. A. Riedell Consultant or advisory role: Abbvie, Novartis, BMS, Janssen, BeiGene, ADC Therapeutics, Takeda Pharmaceutical Company, Kite Pharma, Inc./Gilead, Sana Biotechnology, Nektar Therapeutics, Nurix Therapeutics, Intellia Therapeutics, CVC Caremark, and Genmab Honoraria: Novartis Research funding: BMS, Kite Pharma, Inc./Gilead, MorphoSys, Calibr, Tessa Therapeutics, Fate Therapeutics, Xencor, and Novartis Pharmaceuticals Corporation Other remuneration: Speaker's Bureau: Kite Pharma, Inc./Gilead S. J. Schuster Consultant or advisory role: Celgene, Nordic Nanvector, Novartis, Acerta Pharma/AstraZeneca, BeiGene, Loxo, Genetech/Roche, Regeneron, Janssen, Legend Biotech, Incyte, MorphoSys, MustangBio Research funding: Novartis, Pharmacyclics, Adaptive Biotechnologies, Merck, Genetech/Roche, Celgene, Juno Therapeutics, Abbvie, Incyte, TG Therapeutics, DTRM Other remuneration: Patent Combination Therapies of CAR T and PD-1 Inhibitors (via University of Pennsylvania with royalties to Novartis) L. Eliason Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb L. Wang Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb S. A. Tuazon Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb S. Ou Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb L. Shi Employment or leadership position: Evidera: BMS paid Evidera for the analysis and writing of the abstract Stock ownership: Employee stocks from PPD and ThermoFisher Scientific X. Ye Employment or leadership position: Employee at Evidera; BMS paid Evidera for the analysis and writing of the abstract S. S. Kenderian Honoraria: Scientific Advisory Boards: Kite, Novartis, Juno, Humanigen, Calibr, Capstan, Luminary Research funding: Novartis, Kite/Gilead, Juno/BMS, Humanigen, Lentigen, MorphoSys, LEAHLabs, Sunesis/Viracta Other remuneration: Patents and Royalties: Novartis, Humanigen, MustangBio, Mettaforge, Sendero; DSMB: Humanigen