Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem; Hadassah Cancer Research Institute and Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem; The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem.
Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem; The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem.
ESMO Open. 2024 Oct;9(10):103715. doi: 10.1016/j.esmoop.2024.103715. Epub 2024 Sep 16.
The increasing use and anticipated future adoption of antibody-drug conjugates (ADCs) present a significant challenge in identifying and monitoring patients for the development of potentially fatal drug-induced interstitial lung disease (ILD). We sought to apply a tissue-specific methylation analysis of circulating cell-free DNA (cfDNA) to measure lung damage in patients with trastuzumab deruxtecan (T-DXd)-related ILD.
We describe a patient with metastatic human epidermal growth factor receptor 2 (HER2)-positive endometrial cancer who developed ILD during T-DXd treatment. Blood samples collected at the time of ILD diagnosis, after recovery, and following rechallenge were studied for lung damage using lung-specific methylation markers in cfDNA. To validate the findings, we also tested plasma samples from an additional cohort of patients with HER2-positive metastatic breast cancer treated with T-DXd.
In patients with HER2-positive metastatic cancer treated with T-DXd, the presence of an active ILD, as assessed clinically and using chest computed tomography, was associated with increased levels of lung-derived cfDNA.
This proof-of-concept study demonstrates that liquid biopsy can be developed as a valuable tool for detecting and monitoring ADC-related ILD. Its low cost and simplicity make it a potential alternative to current imaging methods, warranting further clinical development.
抗体药物偶联物（ADC）的使用不断增加，预计未来将得到更多应用，这对识别和监测可能发生致命性药物性间质性肺病（ILD）的患者提出了重大挑战。我们试图应用循环无细胞 DNA（cfDNA）的组织特异性甲基化分析来测量曲妥珠单抗 deruxtecan（T-DXd）相关 ILD 患者的肺损伤。
我们描述了一例转移性人表皮生长因子受体 2（HER2）阳性子宫内膜癌患者，在接受 T-DXd 治疗期间发生了 ILD。在 ILD 诊断时、恢复后和再次挑战时采集的血液样本，使用 cfDNA 中的肺特异性甲基化标志物来研究肺损伤。为了验证这一发现，我们还测试了来自另一组接受 T-DXd 治疗的 HER2 阳性转移性乳腺癌患者的血浆样本。
在接受 T-DXd 治疗的 HER2 阳性转移性癌症患者中，临床和胸部计算机断层扫描评估的活动性 ILD 与肺来源 cfDNA 水平升高相关。
这项概念验证研究表明，液体活检可以开发为检测和监测 ADC 相关 ILD 的有价值工具。其低成本和简单性使其成为当前成像方法的潜在替代方法，值得进一步临床开发。
