Carfilzomib-induced thrombotic microangiopathy: A case based review

Jindal, Nishant; Jandial, Aditya; Jain, Arihant; Lad, Deepesh; Prakash, Gaurav; Khadwal, Alka; Nada, Ritambhra; Sethi, Jasmine; Ahluwalia, Jasmina

doi:10.1016/j.hemonc.2020.07.001

Cited by 9 publications

(9 citation statements)

References 15 publications

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“…In direct contrast to this, bortezomib has actually previously been reported to induce remission in idiopathic TTP 84 . The pathophysiology of proteasome inhibitor‐induced TMA has not been fully established, nor have optimal treatment strategies been ascertained; thus, improved insights into the biological processes underpinning this effect are of direct clinical relevance 1,76,85,86 . Others have suggested an immune mediated mechanism for proteasome inhibitor‐induced TMA with Moore and Romeril describing a case of bortezomib‐induced TMA/TTP where ADAMTS‐13 levels were in fact found to be reduced at 12% 79 .…”

Section: Thrombotic Microangiopathy In Multiple Myelomamentioning

confidence: 99%

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies

Comerford

Glavey

Quinn

et al. 2022

Journal of Thrombosis and Haemostasis

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Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality, highlighting an unmet clinical need to improve understanding of the pathophysiology of CAT. Multiple myeloma (MM) is associated with one of the highest rates of thrombosis despite widespread use of thromboprophylactic agents. The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including raised von Willebrand factor (VWF) levels, activated protein C resistance, impaired fibrinolysis, and abnormal thrombin generation. In addition, the toxic effect of anti‐myeloma therapies on the endothelium and contribution to thrombosis has been widely described. Elevated VWF/factor VIII (FVIII) plasma levels have been reported in heterogeneous cohorts of patients with MM and other hematological malignancies. In specific studies, high plasma VWF levels have been shown to associate with VTE risk and reduced overall survival. While the mechanisms underpinning this remain unclear, dysregulation of the VWF and A Disintegrin And Metalloprotease Thrombospondin type 1, motif 13 (ADAMTS‐13) axis is evident in certain solid organ malignancies and correlates with advanced disease and thrombosis. Furthermore, thrombotic microangiopathic conditions arising from deficiencies in ADAMTS‐13 and thus an accumulation of prothrombotic VWF multimers have been reported in patients with MM, particularly in association with specific myeloma therapies. This review will discuss current evidence on the pathophysiological mechanisms underpinning thrombosis in MM and in particular summarize the role of VWF/FVIII in hematological malignancies with a focus on thrombotic risk and emerging evidence for contribution to disease progression.

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Section: Thrombotic Microangiopathy In Multiple Myelomamentioning

confidence: 99%

The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies

Comerford

Glavey

Quinn

et al. 2022

Journal of Thrombosis and Haemostasis

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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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“…Most cases of carfilzomibinduced TMA have been reported during the second or third cycle of therapy but the complication can occur at any stage. The onset of carfilzomib-induced TMA is sudden with a deterioration in general condition, anemia, mild thrombopenia, worsening of preexisting hypertension, appearance or worsening of preexisting proteinuria, acute kidney injury, and rarely extrarenal manifestations [2,3].…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have shown that immediate discontinuation of carfilzomib plus supportive care may be sufficient to improve the manifestations of the disease. There is limited evidence that eculizumab, a monoclonal antibody against the complement protein C5, could be beneficial in patients with carfilzomib-induced TMA [3,[6][7][8]. The involvement of activation of the alternative pathway of the complement is an argument for the use of eculizumab in carfilzomib-induced TMA.…”

Section: Discussionmentioning

confidence: 99%