OUT OF THE FRYING PAN AND INTO THE FIRE: A RARE CASE OF DASATINIB-INDUCED PULMONARY ARTERIAL HYPERTENSION

Abstract

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Dasatinib is a tyrosine kinase inhibitor used to treat Ph+ acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia. Dasatinib inhibits SRC kinases involved with regulation of vasodilation and vascular proliferation. Rarely, it is associated with pulmonary arterial hypertension (PAH) in 0.45% of patients. We describe a case of new-onset PAH caused by maintenance dasatinib therapy for Ph+ B-cell ALL. CASE PRESENTATION: A 38 year old male with B-ALL status:post allogeneic stem cell transplantation on dasatinib for 15 months presented to the ER with worsening dyspnea, leg swelling and syncopal episodes for 2 months. He had no history of smoking, HIV, drug abuse, weight loss medications, clotting disorders, or sleep-disordered breathing. Labs showed BNP of 3700 and normal hematological, renal and liver function. Autoimmune testing including antinuclear, anti-mitochondrial, anti-citrullinated peptide and scleroderma antibodies was negative. Pulmonary function tests had isolated reduction in DLCO (49%). Echocardiogram (Echo) revealed severely dilated right ventricle (RV) with severely reduced right ventricular systolic function (RVSF), right ventricular systolic pressure (RVSP) 86 mmHg and normal left ventricular size and function. Echo was normal 1 year ago. CT angiogram was negative for pulmonary embolism with normal lung parenchyma. Right heart catheterization (RHC) showed mean pulmonary artery pressure (mPAP) of 45 mmHg, pulmonary capillary wedge pressure (PCWP) of 14 mmHg, cardiac output(CO) of 5.5 L/min, and pulmonary vascular resistance (PVR) of 5.6 Wood Units. Dasatinib was stopped and subcutaneous treprostinil and diuretic was initiated. Symptoms improved significantly and RHC in 3 months showed remarkable improvement with mPAP 6 mmHg, PCWP 5 mmHg, CO 5.85 L/min and PVR of 0.18. Echo improved with only mildly dilated RV, mildly decreased RVSF. Treprostinil was transitioned to oral macitentan and sildenafil. DISCUSSION: Dasatinib-induced PAH can be severe and irreversible in upto 37% of patients. Given that it can occur any time from 1 week to 75 months after starting therapy, a high index of suspicion is required to recognize this rare but potentially disastrous complication, regardless of duration of therapy. It can be challenging to identify PAH in a dyspneic patient with other, more common, pulmonary complications of dasatinib such as pleural effusion, which occurs in 35% of patients. CONCLUSIONS: Early recognition and treatment of dasatinib-induced PAH has implications for recovery and quality of life as discontinuation of the offending agent leads to resolution of PAH in the majority of patients. PAH specific therapy with pulmonary vasodilators may be warranted in severe disease with symptoms and RV dysfunction. Reference #1: El-Dabh A, Acharya D. Pulmonary hypertension with dasatinib and other tyrosine kinase inhibitors. Pulmonary Circulation. 2019;9(3):204589401986570. Reference #2: Montani D, Bergot E, Günther S et al. Pulmonary Arterial Hypertension in Patients Treated by Dasatinib. Circulation. 2012;125(17):2128-2137. Reference #3: Shah NP, Wallis N, Farber HW et al. Clinical features of pulmonary arterial hypertension in patients receiving dasatinib. American Journal of Hematology. 2015;90(11):1060-1064. DISCLOSURES: No relevant relationships by Abdul Khan, source=Web Response No relevant relationships by Nehan Sher, source=Web Response no disclosure on file for Ramachandra Sista; No relevant relationships by Daniel Yu, source=Web Response