Cardiovascular Organ Damage and Blood Pressure Levels Predict Adverse Events in Multiple Myeloma Patients Undergoing Carfilzomib Therapy

Abstract

Carfilzomib is a second-generation proteasome inhibitor approved for the treatment of multiple myeloma (MM). It seems to determine cardiovascular toxicity, primarily arterial hypertension. No predictive factors for cardiovascular adverse events (CVAEs) are known in patients affected by multiple myeloma treated with carfilzomib. We evaluated the role of cardiovascular organ damage parameters to predict CVAEs in MM patients taking carfilzomib. Seventy patients affected by MM were prospectively enrolled. A comprehensive cardiovascular evaluation was performed before carfilzomib therapy; they underwent a transthoracic echocardiogram and the assessment of carotid-femoral pulse wave velocity. All the patients were followed up (FU) to determine the incidence of CVAEs. The mean age was 60.3 ± 8.2, and 51% were male. The median FU was 9.3 (4.3; 20.4) months. A proportion of 33% experienced CVAEs, 91% of them had uncontrolled hypertension, 4.5% acute coronary syndrome, and 4.5% cardiac arrhythmias. Subjects with CVAEs after carfilzomib treatment had significantly higher blood pressure values, left ventricular mass (98 ± 23 vs. 85 ± 17 g/m2, p = 0.01), and pulse wave velocity (8.5 ± 1.7 vs. 7.5 ± 1.6 m/s, p = 0.02) at baseline evaluation compared to the others. Furthermore, baseline uncontrolled blood pressure, left ventricular hypertrophy, and pulse wave velocity ≥ 9 m/s were able to identify patients at higher risk of developing CVAEs during FU. These preliminary findings indicate that blood pressure control, left ventricular mass, and pulse wave velocity may predict CVAEs in MM patients treated with carfilzomib.

Real‐world experience of carfilzomib‐associated cardiovascular adverse events: SEER‐Medicare data set analysis

“…There was no association between drug dose, infusion time, and concurrent drugs or fluids administered with carfilzomib but elevated natriuretic peptide was associated with increased risk of CVAEs. Similarly, 33% of patients experienced CVAEs in the study by Bruno et al and baseline uncontrolled blood pressure, left ventricular hypertrophy, and higher pulse‐wave velocity were identified as risk factors 15 …”

“…Similarly, 33% of patients experienced CVAEs in the study by Bruno et al and baseline uncontrolled blood pressure, left ventricular hypertrophy, and higher pulse-wave velocity were identified as risk factors. 15 Cardiovascular adverse events remains the drug limiting toxicity of carfilzomib and NCCN also alerts for potential carfilzomib related cardiac and pulmonary toxicity, especially in elderly patients. As the median age for diagnosis of MM is 70 years, nearly two-thirds of patients have preexisting cardiovascular disease at baseline, hence, at risk of developing carfilzomib associated CVAEs.…”

A real‐world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma

“…Considering the increased risk of CVAEs during K treatment 17–21 and the recommended preventive measures, 22,26 a detailed medical and pharmacological history of the patients was recorded before the start of treatment: a cardiac risk factor was identified in 99 patients (50%), among whom arterial hypertension figured most frequently (40%). Seven patients (8%) had an abnormal (over 322 pg/ml) N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), six (6%) had a left ventricular dysfunction (ejection fraction < 55%), four (4%) had an history of coronary artery disease and only one (1%) had a diagnosis of AL amyloidosis without cardiac involvement.…”

“…All adverse events (AEs) were recorded using the Common Terminology Criteria for Adverse Events version 5.0. A focus was reserved for cardio‐vascular AEs (CVAEs), due to the reported relationship between K and cardiac complications 17–22 . RI was defined as estimated glomerular filtration rate (eGFR) ≤ 60 ml/min.…”

The Association between Metabolic Syndrome and Multiple Myeloma

“…This was also confirmed by Patel and Cornell [54], who also reviewed increased cardiovascular complications in MM, in part related to insulin resistance, DM, and dyslipidaemia in addition to hypertension. However, it is of course also possible that certain therapies used in MM such as steroids and the selective proteasome inhibitor carfilzomib may also evoke hypertension in some patients [55, 56].…”