Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature

Bethany E Monteith; Christopher P Venner; Donna E Reece; Andrea K Kew; Marc Lalancette; Jocelyn S Garland; Lois E Shepherd; Joseph L Pater; Annette E Hay

doi:10.1016/j.clml.2020.04.014

Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature

Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):e791-e800. doi: 10.1016/j.clml.2020.04.014. Epub 2020 Apr 30.

Authors

Bethany E Monteith¹, Christopher P Venner², Donna E Reece³, Andrea K Kew⁴, Marc Lalancette⁵, Jocelyn S Garland⁶, Lois E Shepherd⁷, Joseph L Pater⁷, Annette E Hay⁸

Affiliations

¹ Cancer Center of Southeastern Ontario, Queen's University, Kingston, ON, Canada; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada. Electronic address: 14bd7@queensu.ca.
² Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
³ Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada.
⁴ The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
⁵ Hôtel-Dieu de Québec, Université Laval, Québec, QC, Canada.
⁶ Kingston Health Sciences Center, Queen's University, Kingston, ON, Canada.
⁷ Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
⁸ Cancer Center of Southeastern Ontario, Queen's University, Kingston, ON, Canada; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.

PMID: 32807717
DOI: 10.1016/j.clml.2020.04.014

Abstract

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.

Keywords: Bortezomib; Carfilzomib; Drug-induced TMA; Hemolytic anemia; Ixazomib.

Publication types

Case Reports
Research Support, Non-U.S. Gov't
Review

MeSH terms

Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Multiple Myeloma / drug therapy*
Multiple Myeloma / pathology
Proteasome Inhibitors / adverse effects*
Proteasome Inhibitors / pharmacology
Proteasome Inhibitors / therapeutic use
Thrombotic Microangiopathies / chemically induced*
Thrombotic Microangiopathies / pathology

Substances

Proteasome Inhibitors

Associated data

ClinicalTrials.gov/NCT02597062