Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy

• Published in: High blood pressure & cardiovascular prevention Vol. 25; no. 2; pp. 209 - 218
• Main Authors: Iannaccone, Andrea, Bruno, G., Ravera, A., Gay, F., Salvini, M., Bringhen, S., Sabia, L., Avenatti, E., Veglio, F., Milan, A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2018; Springer Nature B.V
• Subjects: Aged; Antineoplastic Agents - adverse effects; Asymptomatic Diseases; Blood pressure; Bortezomib - adverse effects; Cardiology; Cardiotoxicity; Cardiovascular disease; Case-Control Studies; Diabetes; Echocardiography, Doppler; Family medical history; Female; Heart rate; Humans; Hypertension; Male; Medicine; Medicine & Public Health; Middle Aged; Morphology; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Multiple Myeloma - enzymology; Oligopeptides - adverse effects; Original Article; Patients; Pharmacotherapy; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Proteasome Inhibitors - adverse effects; Risk Factors; Software; Statistical analysis; Toxicity; Treatment Outcome; Ventricular Dysfunction, Left - chemically induced; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - physiopathology; Ventricular Function, Left - drug effects; United States > US; Carfilzomib; Global longitudinal strain; Cardiovascular toxicity; Proteasome inhibitors; Multiple myeloma
• ISSN: 1120-9879; 1179-1985
• DOI: 10.1007/s40292-018-0256-1

Introduction Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib. Aim To assess the cardiovascular damage in patients treated with PI for RRMM. Methods 28 consecutive subjects treated with PI for RRMM were evaluated and compared with a population of 22 control (Con) subjects, matched for age, sex and mean 24 h blood pressure (24hMBP). All individuals underwent trans-thoracic echocardiography, ambulatory blood pressure monitoring and pulse wave velocity (PVW) study. Results PI patients did not have significant differences in blood pressure load and PWV compared to controls. Among echocardiographic parameters, the global longitudinal strain (GLS) was significantly decreased in PI subjects (p = 0.02). The GLS was significantly lower also considering only patients treated with carfilzomib. Moreover, among carfilzomib patients, we found increase values of left ventricle mass indexed by BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and morphological and functional parameters of LV, treatment with PI and carfilzomib were significantly associated with GLS (p = 0.01; p = 0.036, respectively). Conclusions PI treatment is associated with subclinical LV dysfunction in patients with RRMM compared to controls, as demonstrated by lower GLS values. These results are confirmed also considering patients treated with carfilzomib. Moreover, in this subgroup of patients, the LVMi is also increased, suggesting higher cardiotoxicity with this treatment.