Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.
Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.
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DOI：
10.1158/2159-8290.cd-21-0538
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发表时间：
2022-03
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影响因子：
28.2
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中科院分区：
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对白血病/淋巴瘤治疗扩展分析 (EXALT) 试验的数据分析表明，基于单细胞功能药物测试的治疗决策指导对于复发性和难治性血液癌是可以实现且有效的。个体化医疗旨在利用个体患者肿瘤的具体特征，将正确的药物与正确的患者相匹配。然而，目前的个性化治疗匹配策略为不到 10% 的癌症患者提供了治疗机会。一种有前景的方法可能是以单细胞分辨率对患者活检标本进行药物分析，以直接量化药物作用。我们前瞻性地测试了基于图像的单细胞功能精准医学 (scFPM) 方法，以指导 143 名晚期侵袭性血液癌症患者的治疗。 56 名患者 (39%) 根据 scFPM 结果接受治疗。中位随访时间为 23.9 个月，30 名患者 (54%) 表现出临床获益，与之前的治疗相比，无进展生存期提高了 1.3 倍以上。 12 名患者（占反应者的 40%）经历了异常反应，其持续时间比其各自疾病的预期时间长三倍。我们的结论是，scFPM 的治疗匹配对于晚期侵袭性血液癌症在临床上是可行且有效的。这是第一个使用功能测定来指导肿瘤学单一疗法的精准医学试验。它说明，对于缺乏标准治疗的患者，基于高内涵测定的 scFPM 在基于每个患者癌症的功能依赖性的临床治疗指导中具有重要价值。 参见 Letai 的相关评论，第 17 页。 290. 本文在本期特稿中突出显示，第 290 页。 275
Analysis of data from the Extended Analysis for Leukemia/Lymphoma Treatment (EXALT) trial revealed that guidance of treatment decisions based on single-cell functional drug testing is achievable and efficacious in relapsed and refractory hematologic cancers. Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275