Monteith Bethany E, Venner Christopher P, Reece Donna E, Kew Andrea K, Lalancette Marc, Garland Jocelyn S, Shepherd Lois E, Pater Joseph L, Hay Annette E
Cancer Center of Southeastern Ontario, Queen's University, Kingston, ON, Canada; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):e791-e800. doi: 10.1016/j.clml.2020.04.014. Epub 2020 Apr 30.
Thrombotic microangiopathy (TMA) is a life-threatening clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and microvascular thrombosis, resulting in ischemia and organ damage. Multiple myeloma (MM) is a neoplasm arising from clonal plasma cells within the bone marrow. The treatment frequently includes multi-agent immunochemotherapy, often with the use of proteasome inhibitors (PIs) such as bortezomib, carfilzomib, or ixazomib. There are increasing reports of TMA in association with PI exposure. This review summarizes the epidemiology, pathogenesis, and diagnosis of PI-related drug-induced TMA. We will outline the definition and diagnosis of TMA and explore an important cause of hemolysis in patients with MM: drug-induced TMA after PI exposure, an increasingly recognized therapeutic complication. This will be emphasized through the description of 3 novel cases of TMA. These illustrative cases occurred after treatment with high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone as part of the MCRN003/MYX1 phase II clinical trial (NCT02597062) in relapsed MM.
血栓性微血管病（TMA）是一种危及生命的临床综合征，其特征为溶血性贫血、血小板减少和微血管血栓形成，进而导致缺血和器官损害。多发性骨髓瘤（MM）是一种起源于骨髓中克隆性浆细胞的肿瘤。其治疗通常包括多药免疫化疗，常使用蛋白酶体抑制剂（PIs），如硼替佐米、卡非佐米或伊沙佐米。与PI暴露相关的TMA报告日益增多。本综述总结了PI相关药物性TMA的流行病学、发病机制和诊断。我们将概述TMA的定义和诊断，并探讨MM患者溶血的一个重要原因：PI暴露后药物性TMA，这是一种越来越被认识到的治疗并发症。这将通过描述3例TMA新病例来强调。这些典型病例发生在复发MM的MCRN003/MYX1 II期临床试验（NCT02597062）中，作为高剂量每周一次卡非佐米、环磷酰胺和地塞米松治疗的一部分。
