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Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel
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Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes

Adrien Joseph1,2, Stéphanie Harel3, Laurent Mesnard2,4,5

  • 1Service de Médecine intensive réanimation, Hôpital Saint Louis, Assistance Publique des Hôpitaux de Paris, Paris, France.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|April 24, 2024
PubMed
Abstract

Insights

Carfilzomib-associated thrombotic microangiopathy (CFZ-TMA) often causes severe acute kidney injury. Complement pathway variants and eculizumab treatment did not appear to influence the prognosis of this rare condition.

Area of Science:

  • Nephrology
  • Hematology
  • Pharmacology

Background:

  • Carfilzomib (CFZ), a proteasome inhibitor for relapsed/refractory myeloma, is linked to thrombotic microangiopathy (CFZ-TMA).
  • The involvement of complement alternative pathway variants and the efficacy of complement blockade (e.g., eculizumab) in CFZ-TMA are not well-defined.

Purpose of the Study:

  • To analyze clinical characteristics, genetic factors, and treatment outcomes in patients with CFZ-TMA.
  • To investigate the role of complement pathway variants and eculizumab in CFZ-TMA pathophysiology and prognosis.

Main Methods:

  • Retrospective analysis of 37 CFZ-TMA cases from a French reference center.
  • Clinical data collection, genetic analysis for complement pathway variants, and assessment of treatment responses.

Main Results:

  • Infections were common triggers; all patients had acute kidney injury (AKI), often severe (KDIGO stage 3).
  • Neurological and cardiac involvement were less frequent. ADAMTS13 and complement activity were normal; no pathogenic complement pathway variants were identified.
  • While TMA resolved in most patients, significant AKI persisted. Treatments like plasma exchange, corticosteroids, and eculizumab showed no significant impact on outcomes.

Conclusions:

  • CFZ-TMA is characterized by severe AKI and frequent long-term renal sequelae.
  • Complement pathway variants and complement blockade therapy do not appear to be major factors in the pathophysiology or prognosis of CFZ-TMA.
Keywords:
carfilzomibcomplementeculizumabmyelomathrombotic microangiopathy

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