Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström’s macroglobulinemia and other malignancies. Proteasome inhibitors act on proteasome peptidases causing proteome instability due to accumulating aggregated, unfolded and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous (IV) irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the reversible PI orally administered ixazomib or IV bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Since PIs are critical components of the treatment of hematological malignancies including AL amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at preclinical level and offering cardio-protection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy and develop new PIs with safe cardiovascular profiles.

JACC CardioOncology Editor-in-Chief and CME Editor
Bonnie Ky, MD, MSCE, FACC

Authors
Georgios Georgiopoulos, MD, PhD

Nikolaos Makris, MD

Efstathios Kastritis, MD, PhD

Kimon Stamatelopoulos , MD, PhD

Important Dates

Date of Release: February 21, 2022
Term of Approval/Date of CME/MOC Expiration: February 20, 2023