Dasatinib-Induced Persistent Pulmonary Arterial Hypertension Treated with Sequential Bosentan and Riociguat Therapy: A Case Report

Abstract

Background: Dasatinib is a tyrosine kinase inhibitor commonly used as first-line treatment for chronic myeloid leukemia (CML). Although pulmonary complications are uncommon, dasatinib has been associated with serious adverse effects, including pulmonary arterial hypertension (PAH). Dasatinib-related PAH is currently categorized within group 1 PAH associated with drugs and toxins. We present a case of persistent PAH that developed during long-term dasatinib therapy and was managed with sequential bosentan and riociguat.
Case Presentation: A 52-year-old woman with chronic-phase CML developed progressive exertional dyspnea and fatigue after 5 years of dasatinib treatment. She also had severe PAH and bilateral pleural effusions. Transthoracic echocardiography revealed right-sided cardiac enlargement, with a tricuspid regurgitation jet velocity of 3.9 m/s. Right heart catheterization confirmed precapillary pulmonary hypertension consistent with group 1 PAH. Thoracic computed tomography demonstrated bilateral pleural effusions. Dasatinib-related PAH was considered the most likely diagnosis; dasatinib was discontinued and replaced with nilotinib. Prednisolone was administered for approximately 4 months for the pleural effusion.
According to the 2022 ESC/ERS pulmonary hypertension guidelines, the patient was classified as being at intermediate risk before initiation of PAH-targeted combination therapy. Bosentan was initially prescribed. Because the clinical and hemodynamic response remained inadequate, riociguat was subsequently added. Following the introduction of riociguat, the patient’s symptoms improved substantially, and the clinical risk status decreased to the low-risk category. Nevertheless, right heart catheterization performed after 1 year of combination treatment demonstrated persistent pulmonary hypertension despite the marked clinical improvement.
Conclusion: Dasatinib is an important therapeutic option for patients with CML but may cause persistent pulmonary vascular abnormalities. Prompt recognition of PAH, withdrawal of dasatinib, and appropriately individualized PAH-directed treatment may lead to substantial clinical and hemodynamic improvement. This case also highlights the possibility that pulmonary vascular abnormalities may persist despite symptomatic recovery.