Health and Economic Impact of Vein-to-Vein Time in CAR T-Cell Therapy in the Second-Line Treatment of Relapsed/Refractory Large B-Cell Lymphoma: A US Cost-Effectiveness Analysis.

Chimeric antigen receptor T-cell (CAR T) therapies are approved in the United States (US) for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). In the CAR T treatment process, a short vein-to-vein time (V2VT) is critical to minimize the likelihood of deterioration from aggressive disease while waiting for infusion. This study evaluated the impact of V2VT on survival and economic outcomes for R/R second-line (2L) axicabtagene ciloleucel (axi-cel) versus lisocabtagene maraleucel (liso-cel) treatment of patients with LBCL in the US. An economic model was developed to evaluate the cost-effectiveness of 2L axi-cel versus liso-cel in patients with R/R LBCL over a 50-yr time horizon from a US third-party payer perspective. The model was comprised of: (1) a decision tree to account for V2VT, and (2) a 3-state partitioned survival model that captured health state transitions. Transition between health states were based on progression-free survival (PFS) and overall survival (OS) data stratified based on long (≥36 d) versus short (<36 d) V2VT. The proportion of axi-cel patients with short and long V2VT was 94% and 6%, respectively, while that for liso-cel was 50% each. Survival data were sourced from the pivotal ZUMA-7 trial and varied for short and long V2VT, where V2VT-specific OS and PFS data were based on reported hazard ratios (HRs). Inputs for healthcare resource utilization, adverse events (AEs), costs, and utilities were sourced from published data or based on assumptions. The model estimated quality-adjusted life years (QALYs), total costs (in 2023 US dollars, $), the incremental cost-effectiveness ratio (ICER), and the net monetary benefit (NMB) at a willingness-to-pay threshold (WTP) of $150,000. Sensitivity and scenario analyses were conducted. Treatment with 2L axi-cel resulted in improved health outcomes compared with 2L liso-cel (incremental QALYs of 0.56) as well as reduced total costs (cost savings of $13,156). Under base case assumptions, 2L axi-cel dominated liso-cel (more effective and less costly) with an NMB of $96,407 for a WTP of $150,000. Key model drivers from one-way sensitivity analyses included OS HRs for short versus long V2VT, axi-cel acquisition costs, and the proportion of patients receiving third-line (3L) treatment. 2L axi-cel was always cost-effective compared with 2L liso-cel in probabilistic sensitivity analyses at a willingness-to-pay threshold of $50,000 per QALY, and 2L axi-cel is cost-saving compared with 2L liso-cel in 88% of the probabilistic sensitivity analysis runs. Results from scenario analyses where AE rates were varied, AEs were individually costed, and where 3L bispecific antibodies were excluded were consistent with base case results. 2L treatment with axi-cel was more effective and less costly compared with liso-cel in patients with LBCL in the US. These findings suggest that reduced V2VT was associated with improved clinical and economic outcomes, and highlight the importance of short V2VT in R/R 2L LBCL CAR T treatments.