Τίτλος:
Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p < 0.01) and FMD decreased at cycles 3 and 6 compared to baseline (p ≤ 0.05). FMD changes were associated with CFZ-induced PrA changes (p < 0.05) and lower PrA recovery during first cycle was associated with more prominent FMD decrease (p = 0.034 for group interaction). During treatment, 25 patients developed Grade ≥3 CVAEs. Low baseline FMD (HR 2.57 lowest vs. higher tertiles, 95% CI 1.081–6.1) was an independent predictor of CVAEs. During treatment, an acute FMD decrease >40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29–11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker. © 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
Συγγραφείς:
Kastritis, E.
Laina, A.
Georgiopoulos, G.
Gavriatopoulou, M.
Papanagnou, E.-D.
Eleutherakis-Papaiakovou, E.
Fotiou, D.
Kanellias, N.
Dialoupi, I.
Makris, N.
Manios, E.
Migkou, M.
Roussou, M.
Kotsopoulou, M.
Stellos, K.
Terpos, E.
Trougakos, I.P.
Stamatelopoulos, K.
Dimopoulos, M.A.
Περιοδικό:
Leukemia Research
Εκδότης:
Springer Nature BV
Λέξεις-κλειδιά:
carfilzomib; proteasome; antineoplastic agent; carfilzomib; dexamethasone; oligopeptide; proteasome, adult; aged; Article; cancer immunotherapy; cardiotoxicity; clinical article; endothelial dysfunction; enzyme activity; female; flow-mediated dilation test; human; male; multiple cycle treatment; prediction; priority journal; prospective study; survival rate; cardiovascular system; clinical trial; drug effect; middle aged; multiple myeloma; vascular disease; vascular endothelium, Aged; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular System; Dexamethasone; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Multiple Myeloma; Oligopeptides; Prospective Studies; Proteasome Endopeptidase Complex; Vascular Diseases
DOI:
10.1038/s41375-021-01141-4
