Carfilzomib-associated renal toxicity is common and unpredictable: a comprehensive analysis of 114 multiple myeloma patients

• Published in: Blood cancer journal (New York) 2020-11, Vol.10 (11), p.109-109, Article 109
• Main Authors: Fotiou, Despina, Roussou, Maria, Gakiopoulou, Charikleia, Psimenou, Erasmia, Gavriatopoulou, Maria, Migkou, Magdalini, Kanellias, Nikolaos, Dialoupi, Ioanna, Eleutherakis-Papaiakovou, Evangelos, Giannouli, Stavroula, Delavinia, Christina, Efstathiou, Kostantinos, Kontogiannis, Sofoklis, Terpos, Evangelos, Dimopoulos, Meletios A., Kastritis, Efstathios
• Format: Article
• Language: English
• Subjects: 692/699/1541/1990/804; 692/700/565/1436/99; 692/700/565/2194; Acute Kidney Injury - chemically induced; Adult; Aged; Aged, 80 and over; Albuminuria - chemically induced; Albuminuria - epidemiology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Female; Glomerulosclerosis, Focal Segmental - chemically induced; Glomerulosclerosis, Focal Segmental - epidemiology; Hematology; Humans; Male; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - epidemiology; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oncology; Targeted cancer therapy
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-020-00381-4

Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed and refractory myeloma (RRMM). Its use has been associated with cardiovascular toxicity but although recently a signal of clinically significant renal complications has also been identified, it is less extensively investigated. We analyzed data of 114 consecutive patients with RRMM who received CFZ-based regimens. Renal complications not related to MM progression were observed in 19 (17%) patients; thrombotic microangiopathy (TMA) was seen in 6 (5%) patients, albuminuria >1 gr/day in 7 patients (6%) and at least grade 3 acute kidney injury (AKI) which could not be otherwise explained in 6 patients (5%). A total of 15 patients discontinued CFZ and dosing was reinitiated at a lower level in one patient with AKI. Albuminuria was associated with focal segmental glomerulosclerosis in the renal biopsy (performed in a total of 6 patients). Renal complications during CFZ therapy are common, occur mostly early and are unpredictable. A potential effect of CFZ on the renal endothelium could be implicated in the pathogenesis of these complications and may also share common pathophysiology with cardiovascular effects of CFZ.