Don't keep me waiting: estimating the lifetime impact of reduced vein-to-vein time for CAR-T treated patients with LBCL.

Sachin Vadgama,Richard T Maziarz,Marcelo C Pasquini,Zhen-Huan Hu,Markqayne D Ray, Harry Smith,Ash Bullement, Mark Edmondson-Jones, Will Sullivan, Guillaume Cartron

Blood advances(2024)

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摘要
Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of hematological cancers. Production requires a complex logistical process from leukapheresis to patient infusion, the vein-to-vein time (V2VT), during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line+ (3L+) relapsed/refractory large B-cell lymphoma (r/r LBCL) patients treated with CAR T. A mathematical model was developed to estimate the lifetime outcomes of a hypothetical cohort of patients who had either a 'long' or 'short' V2VT. Life-years (LYs), quality-adjusted life years (QALYs), and costs were estimated. Scenario analyses were performed to assess the robustness of results to key assumptions.  The results of the model show that reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3.2-year gain in life expectancy (4.2 vs 7.7 LYs), and 2.4 additional QALYs (3.2 vs 5.6) per patient. Furthermore, a shorter V2VT was shown to be cost-effective under conventional willingness-to-pay thresholds in the United States. Results are driven by a higher infusion rate and and a better efficacy of CAR T-cell therapy for those infused. Scenario analyses using a smaller difference in V2VT (24 vs 36 days) produced consistent results. Our study is the first to quantify lifetime V2VT-related outcomes for 3L+ r/r LBCL patients treated with CAR T utilizing currently available evidence. Shorter V2VTs led to improved outcomes, demonstrating the importance of timely infusion achievable by faster manufacturing times and optimization of hospital delivery.
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