以循环肿瘤组分的动态变化预测接受免疫疗法治疗的实体瘤恶性肿瘤患者的实际临床结果

IF 3.2 Q2 ONCOLOGY Oncology and Therapy Pub Date : 2024-09-01 Epub Date: 2024-07-22 DOI:10.1007/s40487-024-00287-2

Ryan D Gentzler, John Guittar, Akash Mitra, Wade T Iams, Terri Driessen, Regina Schwind, Michelle M Stein, Kristiyana Kaneva, Seung Won Hyun, Yan Liu, Adam J Dugan, Cecile Rose T Vibat, Chithra Sangli, Jonathan Freaney, Zachary Rivers, Josephine L Feliciano, Christine Lo, Kate Sasser, Rotem Ben-Shachar, Halla Nimeiri, Jyoti D Patel, Aadel A Chaudhuri

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引用次数: 0

摘要

导言：能够确定免疫检查点抑制剂（ICI）疗法早期疗效的动态分子生物标志物仍是一项尚未满足的临床需求。在此，我们评估了一种用于治疗反应监测（TRM）的新型循环肿瘤DNA（ctDNA）检测方法xM（量化ctDNA肿瘤组分（TF）的变化）能否预测在真实世界（RW）队列中接受ICI单药或联合化疗患者的疗效：这项回顾性研究包括Tempus去标识化临床基因组数据库中接受纵向液基新一代测序的晚期癌症患者。符合条件的患者在开始接受 ICI 治疗前至少 40 天采集血液样本，并在开始接受 ICI 治疗后 15-180 天采集治疗中的血液样本。TF通过集合算法计算，该算法利用变异和拷贝数信息得出的TF估计值。分子反应（MR）患者被定义为两次检测之间 TF 下降≥ 50%的患者。在 ICI 启动后 2 到 18 周之间有 rw-imaging 数据的患者子集中，将 MR 和 rw-imaging 的预测价值与单独的 rw-imaging 模型进行了比较：可评估组群（N = 86）由 14 种实体癌类型组成。患者接受了 ICI 单药治疗（38.4%，N = 33）或 ICI 联合化疗（61.6%，N = 53）。与分子无应答（nMR）患者相比，MR患者的rw总生存期（rwOS）（危险比（HR）0.4，P = 0.004）和rw无进展生存期（rwPFS）（HR 0.4，P = 0.005）明显更长。ICI 单一疗法亚组中也出现了类似的结果；rwOS 的 HR 为 0.2，P = 0.02；rwPFS 的 HR 为 0.2，P = 0.01。在具有匹配 rw-imaging 数据的患者子群（N = 51）中，结合 MR 和 rw-imaging 的模型在预测 rwOS 方面优于单独的 rw-imaging 模型（P = 0.02）。

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Dynamic Changes in Circulating Tumor Fraction as a Predictor of Real-World Clinical Outcomes in Solid Tumor Malignancy Patients Treated with Immunotherapy.

Introduction: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort.

Methods: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15-180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone.

Results: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02).

Conclusions: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy.

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来源期刊

Oncology and Therapy ONCOLOGY-

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6 weeks

期刊介绍： Now indexed in PubMed Aims and Scope Oncology and Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Oncology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. 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