‘Don’t keep me waiting’: estimating the impact on lifetime survival and QALYs of reduced vein‐to‐vein time for LBCL patients treated with CAR T in the 3L+ setting (2023)

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the treatment of haematological cancers. However, production requires a complex multistep process from leukapheresis, manufacturing, transport and storage before final infusion. This time is known as the vein-to-vein time (V2VT) during which the patient’s condition may deteriorate, thus highlighting the potential importance of V2VT on patients outcome. This modelling study was designed to compare potential outcomes of a ‘long’ versus ‘short’ V2VT for relapsed/refractory large B-cell lymphoma (r/r LBCL) patients treated with CAR T-cell therapy in the 3L+ setting. Methods: A hypothetical cohort of patients enter a decision tree model at leukapheresis, they are then assigned a probability of successful infusion based on V2VT. Patients then enter a partition survival model which estimates life-years (LYs) and quality-adjusted life years (QALYs) over a lifetime horizon, which were based on real world axi-cel OS data. Other CAR T efficacy data were not included to provide conservative estimates and to avoid confounding. Model inputs were sourced from the published literature and the ZUMA-1 trial. An epidemiological model was used to extrapolate results to CAR T-eligible US patients. Finally, scenario analyses were performed to assess the robustness of results to key assumptions. Results: Reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3-year gain in life expectancy (4.2 vs. 7.7 LYs), and an additional 2 QALYs (2.9 vs. 5.3) per patient. This translates to 9,328 additional LYs and 6,385 additional QALYs every year, if all ≈ 2,710 eligible patients in the US received a ‘short’ V2VT. Using a smaller difference in V2VT (24 vs. 37 days [liso-cel median V2VT; TRANSCEND-NHL-001]) produced 2.6 and 1.8 additional LYs and QALYs, respectively, equating to population level gains of 7,040 LYs and 4,819 QALYs (Figure 1). Outcomes were consistently positive across all sensitivity analyses. The research was funded by: Kite, A Gilead Company Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Genomics, Epigenomics, and Other -Omics Conflicts of interests pertinent to the abstract. R. Maziarz Employment or leadership position: Oregon Health & Science University Consultant or advisory role: Novartis, Artiva Stock ownership: Abbvie, BMS, Artiva, Pfizer, (all managed by independent financial advisor) Honoraria: Kite, Allovir, Incyte, Novartis Research funding: BMS, Orca, Novartis S. Vadgama Employment or leadership position: Kite Stock ownership: Gilead M. Pasquini Consultant or advisory role: Bristol Myers Squibb Honoraria: Bristol Myers Squibb Research funding: Bristol Myers Squibb, Kite Pharma, Novartis, Janssen Z. Hu Employment or leadership position: Kite M. Ray Employment or leadership position: Kite H. Smith Employment or leadership position: Kite A. Bullement Research funding: Kite M. Edmondson-Jones Research funding: Kite W. Sullivan Research funding: Kite G. Cartron Consultant or advisory role: Roche, MabQi, Ownards Therapeutics Honoraria: Gilead, Novartis, Jansen, Abbvie, BMS Travel grants: Roche, Gilead, Novartis, Jansen