CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:"Don't keep me waiting": estimating the impact of reduced vein-to-vein time on lifetime US 3L+ LBCL patient outcomes.
"Don't keep me waiting": estimating the impact of reduced vein-to-vein time on lifetime US 3L+ LBCL patient outcomes.
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CAR-T 细胞疗法已革新血液系统恶性肿瘤治疗,但其生产流程复杂,从白细胞单采到输注患者的“静脉到静脉时间”(V2VT)可能较长,期间患者临床状况可能恶化。
本研究旨在估算缩短 V2VT 对接受三线及以上治疗(3L+)的复发/难治性大 B 细胞淋巴瘤(R/R LBCL)CAR-T 患者的获益。研究建立数学模型,估算一组假设患者在 V2VT 较长或较短时的终身结局,包括生命年(LY)、质量调整生命年(QALY)和成本,并通过情景分析评估关键假设对结果稳健性的影响。模型显示,将 V2VT 从 54 天(替沙仑赛中位 V2VT;JULIET)缩短至 24 天(阿基仑赛中位 V2VT;ZUMA-1),可使每位患者预期寿命增加 3.2 年(4.2 对 7.7 LY),并增加 2.4 个 QALY(3.2 对 5.6)。在美国常用支付意愿阈值下,较短 V2VT 具有成本效果。获益主要由更高输注率以及接受输注患者的更好疗效所驱动。将 V2VT 差异设为较小的 24 对 36 天时,情景分析结果仍一致。
本研究首次利用现有证据量化 3L+ R/R LBCL CAR-T 患者 V2VT 相关终身结局。较短 V2VT 可改善结局,说明通过加快生产并优化医院交付流程,确保及时输注十分重要。
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.
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