Bibliographic Details
| Title: |
Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes. |
| Authors: |
Joseph, Adrien, Harel, Stéphanie, Mesnard, Laurent, Rafat, Cédric, Knapp, Silène, Rumpler, Anne, Philipponnet, Carole, Barba, Christophe, Rebibou, Jean-Michel, Buob, David, Hertig, Alexandre, Vargaftig, Jacques, Halimi, Jean-Michel, Arnulf, Bertrand, Bretaud, Anne-Sophie, Joly, Bérangère, Grangé, Steven, Coppo, Paul |
| Source: |
Nephrology Dialysis Transplantation; Dec2024, Vol. 39 Issue 12, p2067-2078, 12p |
| Subject Terms: |
SARS-CoV-2, PLASMA exchange (Therapeutics), ACUTE kidney failure, PROGNOSIS, PROTEASOME inhibitors |
| Abstract: |
Background Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined. Methods We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments. Results A trigger was identified in more than half of cases, including eight influenza and five severe acute respiratory syndrome coronavirus-2 cases. All patients presented with acute kidney injury (AKI) [KDIGO stage 3 in 31 (84%) patients] while neurological (n = 13, 36%) and cardiac (n = 7, 19%) damage were less frequent. ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) and complement activity were normal (n = 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested. TMA resolved in most (n = 34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However, none of these treatments demonstrated a significant impact on outcomes. Conclusion This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
