Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes.
Nephrol Dial Transplant
; 2024 Apr 24.
Article
in En
| MEDLINE
| ID: mdl-38658194
ABSTRACT
BACKGROUND AND HYPOTHESIS:
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 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Nephrol Dial Transplant
Journal subject:
NEFROLOGIA
/
TRANSPLANTE
Year:
2024
Type:
Article
Affiliation country:
France