Pulmonary hypertension (PH) in patients (pts) with CML treated with tyrosine kinase inhibitors (TKIs).

Abstract

6597 Background: TKIs are the current standard therapy for patients with CML. Fluid retention and pleural effusions have been reported in pts treated with TKIs, particularly with dasatinib. Although TKIs have been shown to reverse PH in animal models, there have been some reports of development of reversible PH with dasatinib. Methods: We conducted a retrospective analysis on 401 CML pts in CP who were treated with TKIs (imatinib, dasatinib or nilotinib) as initial therapy for CML and had a transthoracic echocardiogram done (TTE) at some point during the course of therapy. PH was diagnosed if the patient had an estimated right ventricular systolic pressure (RVSP) of 35 mm Hg or greater. Secondary causes of PH (systolic or diastolic dysfunction on TTE, chronic obstructive pulmonary diseases [COPD], obstructive sleep apnea [OSA] and pulmonary embolism) were investigated during chart review. Results: Twenty pts had at least one TTE; median age 57 years, 46% males. Six pts (30%) received nilotinib 400 mg BID, 4 (20%) pts imatinib (400 mg; n = 1, 600 mg; n = 1 and 800 mg daily; n = 2), and 10 (50%) pts received dasatinib (dose between 40 mg to 140 mg daily). Five (25%) pts had coronary artery disease, 9 (45%) pts had systemic hypertension, 2 (10%) pts had COPD and 3 (15%) pts had OSA. Thirteen pts had serial TTE to compare the progression of PH including 6 (7%) who had a TTE prior to starting TKI. Among these 13 pts with serial TTE, 7 had rising RVSP with one patient having mild global hypokinesia, another with diastolic dysfunction and another with OSA. Four of those 7 patients had normal RVSP on their TTE prior to starting therapy. Five other pts had improvement in the RVSP on serial TTE, 4 of them with systemic hypertension. Two of those 5 pts had elevated RVSP on their TTE prior to starting therapy. One pt had no change. Eleven pts had pleural effusions (7 dasatinib, 3 imatinib, 1 nilotinib) associated with PH. Conclusions: TKI therapy is occasionally associated with development of PH, but RVSP may improve spontaneously in some pts. A prospective study is needed to further investigate the relationship between TKIs and the development of PH. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis