Carfilzomib-induced pulmonary hypertension in a patient with multiple myeloma

Abstract

A 59-year-old female being treated for multiple myeloma (MM) was referred to the Division of Cardiology due to edema and dyspnea. She developed dyspnea on exertion 2 months previously when carfilzomib, a second-generation selective proteasome inhibitor which was approved for treatment of relapsed and refractory MM, was introduced, and facial edema appeared thereafter. The electrocardiogram showed sinus rhythm with T-wave inversion on extensive leads and the chest X-ray showed cardiomegaly. Although cancer therapeutics-related cardiac dysfunction was assumed to be the complication, echocardiogram revealed no evidence of elevated left ventricular filling pressure whereas elevated tricuspid regurgitation velocity (3.2 m/s) with right ventricular systolic dysfunction suggested pre-capillary pulmonary hypertension (PH). Right heart catheterization demonstrated elevated mean pulmonary artery pressure (33 mmHg) along with high pulmonary vascular resistance (11.54 Wood Units) and normal pulmonary capillary wedge pressure (9 mmHg), confirming the echocardiographic findings. After ruling out other causes, PH associated with carfilzomib was diagnosed. Cessation of carfilzomib along with pulmonary vasodilator therapy led to improvement of symptoms and reduction of right heart size along with reduced estimated pulmonary systolic pressure 2 months later. Although carfilzomib-induced PH is rare, we need to consider its possibility when we find PH in patients receiving carfilzomib.

Learning objective: While adverse cardiovascular events are often found in patients with multiple myeloma (MM) after use of carfilzomib, the occurrence of pulmonary hypertension (PH) is reported to be rare. Because temporal association of echocardiographic findings to carfilzomib therapy plays a key role for the diagnosis of drug-associated PH, serial echocardiographic examinations should be performed when we start carfilzomib therapy in refractory MM patients.

Keywords: Carfilzomib; Echocardiography; Multiple myeloma; Pulmonary hypertension.