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血液淋巴系统恶性肿瘤靶向治疗的皮肤不良事件

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

作者信息

Ransohoff Julia D, Kwong Bernice Y

机构信息

Department of Dermatology, Stanford University School of Medicine, Stanford, CA.

Department of Dermatology, Stanford University School of Medicine, Stanford, CA.

出版信息

Clin Lymphoma Myeloma Leuk. 2017 Dec;17(12):834-851. doi: 10.1016/j.clml.2017.07.005. Epub 2017 Jul 14.

Abstract

The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. We systematically review according to drug-targeting pathway the cutaneous AE profiles of these drugs, and offer insight when possible into whether pharmacologic target versus immunologic modulation primarily underlie presentation. We include discussion of tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib), blinatumomab, ibrutinib, idelalisib, anti-B cell antibodies (rituximab, ibritumomab, obinutuzumab, ofatumumab, tositumomab), immune checkpoint inhibitors (nivolumab, pembrolizumab), alemtuzumab, brentuximab, and proteasome inhibitors (bortezomib, carfilzomib, ixazomib). We highlight skin reactions seen with antiliquid but not solid tumor agents, draw attention to serious cutaneous AEs that might require therapy modification or cessation, and offer management strategies to permit treatment tolerability. We emphasize the importance of early diagnosis and treatment to minimize disruptions to care, optimize prognosis and quality of life, and promptly address life-threatening skin or infectious events. This evolving partnership between oncologists and dermatologists in the iterative characterization and management of skin toxicities will contribute to a better understanding of these drugs' cutaneous targets and improved patient care.

摘要

液体肿瘤致癌驱动因素的识别促使具有不同皮肤不良事件(AE)特征的靶向药物迅速发展。这些皮肤毒性的诊断和管理促使皮肤科医生和肿瘤学家在建立支持性肿瘤皮肤病诊所方面建立了新的合作关系。在本文中,我们回顾了在血液和淋巴系统恶性肿瘤靶向治疗期间观察到的最常见且重要的皮肤不良事件的临床表现、机制和管理的当前知识状态。我们根据药物靶向途径系统地回顾了这些药物的皮肤AE特征,并尽可能深入了解药物靶点与免疫调节在主要表现中所起的作用。我们讨论了酪氨酸激酶抑制剂(伊马替尼、达沙替尼、尼洛替尼、博舒替尼、波纳替尼)、博纳吐单抗、伊布替尼、艾代拉里斯、抗B细胞抗体(利妥昔单抗、碘[131I]托西莫单抗、奥滨尤妥珠单抗、奥法木单抗、托西莫单抗)、免疫检查点抑制剂(纳武单抗、派姆单抗)、阿仑单抗、本妥昔单抗和蛋白酶体抑制剂(硼替佐米、卡非佐米、伊沙佐米)。我们强调了抗液体肿瘤而非实体肿瘤药物出现的皮肤反应,提请注意可能需要调整或停止治疗的严重皮肤不良事件,并提供管理策略以提高治疗耐受性。我们强调早期诊断和治疗的重要性,以尽量减少对治疗的干扰,优化预后和生活质量,并及时处理危及生命的皮肤或感染事件。肿瘤学家和皮肤科医生在皮肤毒性的迭代特征描述和管理方面不断发展的合作关系,将有助于更好地理解这些药物的皮肤靶点并改善患者护理。

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