Abstract Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical
Background: Autologous chimeric antigen receptor (CAR) T-cell products are manufactured using individual patient cells, leading to variable time between leukapheresis and infusion, or vein-to-vein time (V2Vt). V2Vt compromises sub-intervals, including time for transportation, manufacturing, and quality release.
Aims: This systematic literature review and meta-analysis describes the heterogeneous V2Vt for axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) in relapsed or refractory large B-cell lymphoma (r/r LBCL).
Methods: Systematic searches of MEDLINE, Embase, CENTRAL, and select conferences were conducted on 5 October 2022. Treatment-specific, non-comparative meta-analyses for each pre–CAR T-cell infusion time interval were generated using median of medians.
Results: A total of 40 studies reported time intervals for axi-cel (n=30), tisa-cel (n=13), and/or liso-cel (n=4) in r/r LBCL. Studies were not mutually exclusive by CAR T-cell product; however, time intervals were evaluated separately by product. V2Vt was the most reported interval. 31 studies reported V2Vt for axi-cel (n=22), tisa-cel (n=10), and/or liso-cel (n=3). Across all studies, axi-cel had the shortest median V2Vt (30.4 days vs 48.4 days for tisa-cel and 35.9 days for liso-cel; Table). Compared with real-world settings, median V2Vt was shorter in clinical trials for axi-cel (25.5 days vs 30.9 days) but not for tisa-cel (52.0 days vs 48.0 days). Liso-cel was only evaluable in clinical trials, where median V2Vt (35.9 days) was longer vs axi-cel in either clinical trial or real-world settings, except in Europe-only studies (38.0 days). Median V2Vt was shorter in US-only vs Europe-only studies for axi-cel (27.0 days vs 38.0 days) and tisa-cel (42.7 days vs 50.5 days).
Prognostic value of time intervals for CAR T-cell therapy with respect to clinical outcomes was evaluated in 8 studies. Meta-analysis was not feasible due to data parameterization; however, one study noted an association between longer V2Vt and reduced effectiveness (Locke et al. ASH 2022; Poster #3345).
Summary/Conclusion: In this meta-analysis of approved CAR T-cell products in r/r LBCL, axi-cel consistently had the shortest V2Vt compared with other products in clinical trial or real-world settings. Further evaluation of the factors impacting V2Vt, and their association with efficacy and other clinical outcomes, are warranted.
Keywords: Systematic review, Cancer immunotherapy, CAR-T, B cell lymphoma