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

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

doi:10.1016/j.clml.2020.04.014

Cited by 13 publications

(3 citation statements)

References 50 publications

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“…The clustered occurrence of our 2 cases is unique from previous reports that describe carfilzomib-induced TMA as a sporadic event (Table 2). 13,[17][18][19][20][21][22][23][24][25][26][27][28] Both immune-mediated and direct toxic effects have been proposed as mechanisms of DITMA, and while our cases do not differentiate between these mechanisms, we considered whether a combined model of initiation, whereby patient or environmental risk factors modulate occurrence of the disease in conjunction with the inciting drug, could explain the clustered occurrence of cases. In this series, drug manufacturing was not a shared risk factor as each patient received carfilzomib from different lot numbers.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Cases of Carfilzomib-Induced Thrombotic Microangiopathy in 2 Patients With Multiple Myeloma

Myall¹

2022

Federal Practitioner

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Background: In patients with multiple myeloma, thrombotic microangiopathy is a rare adverse event associated with proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib. Case Presentation: Two patients with multiple myeloma who presented with carfilzomib-induced thrombotic microangiopathy received eculizumab with subsequent stabilization of renal function.Conclusions: Given the overall rarity of this adverse event, the simultaneous presentation of these 2 cases was unexpected. These cases underscores the need for heightened awareness in clinical practice of thrombotic microangiopathy. The potential role of eculizumab as a therapeutic treatment in the setting of thrombotic microangiopathy requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Simultaneous Cases of Carfilzomib-Induced Thrombotic Microangiopathy in 2 Patients With Multiple Myeloma

Myall¹

2022

Federal Practitioner

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“…TMA is not limited to the kidney and supportive treatment, including renal replacement therapies and blood transfusions, is needed, as well as a cessation of PI and any other offending agent. TMA seems to be more frequent in patients on carfilzomib than in those on bortezomib according to the literature [65].…”

Section: Target Cancer Agentsmentioning

confidence: 99%

Onconephrology: Update in Anticancer Drug-Related Nephrotoxicity

García-Carro

Draibe

Soler³

2022

Nephron

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The relation that connects cancer and renal damage is bidirectional and this renal damage worsens quality of life and increases morbidity in high-complexity patients such as patients with cancer and kidney injury. Strikingly, in the last decade, the treatment of advanced cancer has clearly advanced in terms of new therapeutic strategies with the ability to transform the advanced metastatic cancer in a chronic condition. In this new era of cancer therapies, cancer treatment including conventional chemotherapy, targeted cancer agents and immunotherapies among others are significantly associated with kidney injury. Renal toxicity that is currently seen in onconephrology departments is in part related to the new therapies such as immunotherapy, and to the prolonged survival achieved at the expense of increasing therapy lines, and a combination of different drugs. In this review, we will discuss in a practical way, nephrotoxicity caused by the main oncospecific treatments such as classical chemotherapy agents, targeted therapies, and immunotherapy. In addition, strategies for prevention and management recommendations in patients with malignancies and kidney disease will also be addressed.

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“…Carfilzomib is a second-generation proteasome inhibitor approved by the US Food and Drug Administration (FDA) in 2012 as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy [7]. Since that time, increasing reports of TMA secondary to carfilzomib have been published [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The most important step in the management of carfilzomibinduced TMA is stopping the drug.…”

Section: Introductionmentioning

confidence: 99%

Carfilzomib-Induced Thrombotic Microangiopathy: Focus on Pathogenesis

2022

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Drug-induced thrombotic microangiopathies present in similar fashion but have varied pathogenic mechanisms. Carfilzomib is an irreversible proteasome inhibitor. Since its initial approval as a single agent for the treatment of relapsed or refractory multiple myeloma in 2012, there have been increasing reports of carfilzomib-induced thrombotic microangiopathy. However, the mechanism of this disease process is not fully understood. Without treatment, there is a high likelihood of end-organ damage, especially in the kidneys, and death. In recent reports, the lifesaving role of eculizumab, a terminal complement inhibitor, in managing and further preventing end-stage renal disease has been described. In this article, we present a case of carfilzomib-induced thrombotic microangiopathy in a patient with multiple myeloma and discuss the pathogenesis of thrombotic microangiopathy in this setting.

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

Cited by 13 publications

References 50 publications

Simultaneous Cases of Carfilzomib-Induced Thrombotic Microangiopathy in 2 Patients With Multiple Myeloma

Simultaneous Cases of Carfilzomib-Induced Thrombotic Microangiopathy in 2 Patients With Multiple Myeloma

Onconephrology: Update in Anticancer Drug-Related Nephrotoxicity

Carfilzomib-Induced Thrombotic Microangiopathy: Focus on Pathogenesis

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