Kite, A Gilead company, Uxbridge, United Kingdom.
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Cancer Center, Milwaukee, WI.
Blood Adv. 2024 Jul 9;8(13):3519-3527. doi: 10.1182/bloodadvances.2023012240.
Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment of hematological cancers. Its production requires a complex logistical process, and the time from leukapheresis to patient infusion (known as the vein-to-vein time [V2VT]) can be long during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line or later (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 LYs (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 a better efficacy of CAR T 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.
嵌合抗原受体 T 细胞疗法(CAR T)彻底改变了血液系统癌症的治疗方式。其生产需要一个复杂的物流过程,从白细胞单采到患者输注(称为静脉到静脉时间[V2VT])的时间可能很长,在此期间患者的临床状况可能会恶化。本研究旨在评估减少 V2VT 对接受 CAR T 治疗的三线或以上(3L+)复发/难治性大 B 细胞淋巴瘤(R/R LBCL)患者的获益。开发了一个数学模型来估计 V2VT 长或短的假设患者队列的终生结果。估计了寿命年(LY)、质量调整寿命年(QALY)和成本。进行了情景分析以评估结果对关键假设的稳健性。模型的结果表明,将 V2VT 从 54 天(tisacel 中位 V2VT;JULIET)缩短至 24 天(axi-cel 中位 V2VT;ZUMA-1)可使预期寿命延长 3.2 年(4.2 与 7.7 LY),每位患者额外获得 2.4 个 QALY(3.2 与 5.6)。此外,在传统的美国支付意愿阈值下,较短的 V2VT 具有成本效益。结果是由输注率较高和 CAR T 的疗效更好驱动的。使用 V2VT 差异较小(24 与 36 天)的情景分析产生了一致的结果。本研究首次利用现有证据量化了接受 CAR T 治疗的 3L+R/R LBCL 患者的终生 V2VT 相关结局。较短的 V2VT 带来了更好的结果,证明了通过更快的制造时间和优化医院交付来实现及时输注的重要性。