基于血液的预后评分及免疫治疗下的早期动态变化，以筛选转移性实体瘤患者继续进行免疫检查点抑制治疗：一项前瞻性纵向研究。
Blood-based prognostic scores and early dynamics under immunotherapy to select patients with metastatic solid tumors for continuing immune check-point inhibition: a prospective longitudinal study.
作者信息
García-Corbacho Javier, Indacochea Alberto, Victoria Iván, Moreno Débora, Angelats Laura, González Navarro Azucena E, Mezquita Laura, Brasó-Maristany Fara, Galván Patricia, Mellado Begoña, Viñolas Nuria, Sauri Tamara, Nogué Miquel, Adamo Barbara, Maurel Joan, Pineda Estela, Gaba Lydia, Reig Oscar, Basté Neus, Sanfeliu Esther, Juan Manel, Prat Aleix, Schettini Francesco
机构信息
The Clinical Trials Unit of Medical Oncology Department, Virgen de la Victoria University Hospital/IBIMA, Campus de Teatinos S/N, 29010, Malaga, Spain.
Programa de Doctorado en Biomedicina, Universitat de Barcelona, Barcelona, Spain.
出版信息
Cancer Immunol Immunother. 2025 Feb 1;74(3):85. doi: 10.1007/s00262-024-03933-w.
INTRODUCTION
Immune check-point inhibitors (ICI) were a major breakthrough in cancer care, but optimal patient selection remains elusive in most tumors.
METHODS
Overall 173 adult patients with metastatic solid tumors candidates to ICI in clinical trials at our Institution were prospectively recruited. Blood samples were collected at cycle 1 (C1D1) and 2 (C2D1) and until the occurrence of progressive disease (PD). C1D1 LIPI, RMH, PMHI, NLR, dNLR, PIPO and GRIm prognostic scores were calculated. The primary endpoint was identifying the best score to predict rapid PD (≤ 4 months) with ICI using logistic regressions accounting for tumor type, and receiving operators characteristics (ROC) with area under curve (AUC), accompanied by an extensive comparison of the score performances in the prediction of overall survival (OS), progression-free survival (PFS), overall response rates (ORR) and durable clinical benefit (DCB). Secondary objectives included describing study cohort outcomes and studying the association between the selected score at C1D1, C2D1 and its dynamics with OS and PFS.
RESULTS
C1D1 LIPI was the best predictor of rapid PD, OS and PFS, regardless of cancer type, compared to other scores. No score was associated to ORR and only RMH to DCB. Baseline LIPI detected three categories of patients with significantly different OS (p < 0.001) and PFS (p = 0.013). The same was observed at C2D1 for OS and PFS (both p = 0.020). Significant LIPI class shifts were observed in the overall population (p < 0.001), rapid progressors (p = 0.029) and non-rapid progressors (p = 0.009). Retaining a good LIPI or experiencing a shift towards a better prognostic class was associated to improved OS (p = 0.009) and PFS (p = 0.006). C2D1 LIPI, but not C1D1, remained significantly associated to rapid PD in multivariable analysis.
CONCLUSIONS
LIPI may improve patient selection for ICI and guide treatment adjustments according to on-treatment dynamics in a pancancer context.
引言
免疫检查点抑制剂（ICI）是癌症治疗领域的一项重大突破，但在大多数肿瘤中，最佳患者选择仍难以确定。
方法
前瞻性招募了在我们机构参加临床试验的173例成年转移性实体瘤患者，这些患者均为ICI治疗的候选对象。在第1周期（C1D1）和第2周期（C2D1）采集血样，直至疾病进展（PD）发生。计算C1D1时的LIPI、RMH、PMHI、NLR、dNLR、PIPO和GRIm预后评分。主要终点是使用考虑肿瘤类型的逻辑回归确定预测ICI治疗后快速PD（≤4个月）的最佳评分，并绘制受试者工作特征曲线（ROC）并计算曲线下面积（AUC），同时广泛比较各评分在预测总生存期（OS）、无进展生存期（PFS）、总缓解率（ORR）和持久临床获益（DCB）方面的表现。次要目标包括描述研究队列的结果，以及研究C1D1、C2D1时选定评分及其动态变化与OS和PFS之间的关联。
结果
与其他评分相比，无论癌症类型如何，C1D1时的LIPI都是快速PD、OS和PFS的最佳预测指标。没有评分与ORR相关，只有RMH与DCB相关。基线LIPI将患者分为三类，其OS（p<0.001）和PFS（p=0.013）有显著差异。C2D1时OS和PFS也观察到同样情况（p均=0.020）。在总体人群（p<0.001）、快速进展者（p=0.029）和非快速进展者（p=0.009）中均观察到LIPI类别有显著变化。维持良好的LIPI或向更好的预后类别转变与OS改善（p=0.009）和PFS改善（p=0.006）相关。在多变量分析中，C2D1时的LIPI与快速PD仍显著相关，而C1D1时的LIPI则不然。
结论
LIPI可能改善ICI治疗的患者选择，并在泛癌背景下根据治疗过程中的动态变化指导治疗调整。
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