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

Despina Fotiou,Meletios A Dimopoulos,Efstathios Kastritis,Erasmia Psimenou,Sofoklis Kontogiannis,Ioanna Dialoupi,Magdalini Migkou,Kostantinos Efstathiou,Christina Delavinia,Stavroula Giannouli,Nikolaos Kanellias,Maria Gavriatopoulou,Charikleia Gakiopoulou,Evangelos Terpos,Maria Roussou,Evangelos Eleutherakis-Papaiakovou

doi:10.1038/s41408-020-00381-4

Despina Fotiou, Meletios A Dimopoulos + Show 14 more

Open Access

https://doi.org/10.1038/s41408-020-00381-4

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Abstract

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.

Highlights

Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed and refractory myeloma (RRMM)
Renal clearance is not a significant pathway for carfilzomib elimination and no dose or treatment schedule adjustments are required in patients with renal impairment[3] but renal toxicity has been described[4]
We report data for 114 consecutive, unselected, RRMM patients who were treated with carfilzomib-based regimens in our center (Department of Clinical Therapeutics, Athens), closely monitored and evaluated for renal complications, including renal biopsies

Summary

Introduction

Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed and refractory myeloma (RRMM). We report data for 114 consecutive, unselected, RRMM patients who were treated with carfilzomib-based regimens in our center (Department of Clinical Therapeutics, Athens), closely monitored and evaluated for renal complications, including renal biopsies. During treatment and up to 30 days after the last carfilzomib dose, 19 (17%) patients developed renal complications (not related to myeloma progression) (Fig. 1).

Results

Conclusion