Carfilzomib‐associated pulmonary arterial hypertension in multiple myeloma

Abstract

Drug-induced pulmonary arterial hypertension (PAH) is constantly evolving as new drugs are developed. Carfilzomib is a recently approved therapy for relapsed and refractory multiple myeloma. While it has been associated with cardiovascular adverse events, such as ischemic heart disease and heart failure, PAH has not been a well-described side effect. We present two patients who developed PAH associated with initiation of carfilzomib. They both initially presented with severe dyspnea, had elevated right ventricular systolic pressure on transthoracic echocardiography and ultimately underwent right heart catheterization. With discontinuation of carfilzomib, both patients had improvement in hemodynamics. However, one patient required initiation of PAH-targeted therapies and has had worsening right ventricular function again despite permanent discontinuation of carfilzomib. It is important to recognize the association between carfilzomib and PAH. Echocardiography can be an important initial screening tool. PAH from carfilzomib therapy may be reversible, especially if diagnosed early, however extended follow up is essential.

Etiology of pulmonary hypertension in multiple myeloma: A case series and literature review

“…Two patients developed pulmonary arterial hypertension after the initiation of carfilzomib for multiple myeloma treatment. Both patients experienced an improvement in pulmonary artery pressures after discontinuation of carfilzomib [7]. However, one patient required initiation of PAH-targeted therapy despite permanent discontinuation of carfilzomib.…”

“…They both had improvement in PA pressures and symptoms with discontinuation of the offending medication (carfilzomib). Notably, several medications used in the treatment of multiple myeloma have been associated with PH, such as carfilzomib and dasatinib, as well as some monoclonal antibodies and immune regulators [7,9]. Dasatinib-induced PAH can improve with discontinuation of the medication, with one study finding improvement in NYHA functional class and pulmonary arterial pressures on repeat right heart catheterization [9].…”

“…However, roughly one-third of patients had persistent PAH even after discontinuation of dasatinib and required long-term targeted PAH therapies [10]. Two additional small case series have shown improvement in hemodynamics with discontinuation of carfilzomib [7,12]. However, similar to dasatinib-induced PAH, there were patients with persistent PAH despite permanent discontinuation of the offending medication.…”

Pulmonary hypertension in patients with multiple myeloma: A comprehensive review

“…In most reports, PH‐MM‐TE related to drug‐induced PAH was reversible while in others both PH and MM were progressive and irreversible. 68 , 72 , 73 , 74 , 75 , 76 , 77 Feyereisn et al also report a case of likely, PH‐MM‐TE treated with Epoprostenol and calcium channel blocker in severe PAH that is vasodilator responsive. 71 Krishnan and colleagues report improvement in functional class and symptoms after institution of PAH treatment with sildenafil and ambrisentan in 3 patients PH‐MM‐TE that developed years after SCT.…”

“…Thalidomide, cyclophosphamide, and carfilzomib are the MM‐targeted chemotherapeutic agents that have been associated with PH the most, while other agents have also been reported to cause PH. In most reports, PH‐MM‐TE related to drug‐induced PAH was reversible while in others both PH and MM were progressive and irreversible 68,72–77 . Feyereisn et al also report a case of likely, PH‐MM‐TE treated with Epoprostenol and calcium channel blocker in severe PAH that is vasodilator responsive 71 .…”