Pulmonary Hypertension in Cancer Patients Treated with Tyrosine Kinase Inhibitors

Abstract

Introduction Cancer patients are at increased risk for pulmonary arterial hypertension (PAH) due to the disease itself, chemo- or radiation therapy, pulmonary embolism, or comorbidities. Several tyrosine kinase inhibitors (TKIs), which are increasingly used in the treatment of various cancers, have been linked with PAH. We aimed to describe the incidence of PAH triggered or worsened by tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia (CML). Methods In this retrospective study, the medical records of all patients with CML who received first line treatment with imatinib, dasatinib, or nilotinib for ≥3 months at a large tertiary cancer center from 2000 to 2017 were reviewed. PAH was defined as a right ventricular systolic pressure >30 mmHg on transthoracic echocardiogram. Patients with PAH were categorized in 3 groups based on the TKI agent used. Descriptive statistics were used for analysis. Results We identified 632 patients who were treated with TKIs for ≥3 months at our institution: 241 (38.1%) dasatinib, 105 (16.6%) nilotinib, 286 (45.3%) imatinib. New or worsened PAH was identified in 83 (13.1%) cases. In the dasatinib PAH group (n=75, 90.4% of all PAH), mean age was 54.95 years and there were 45 (60%) women. In the nilotinib PAH group (n=3, 6% of all PAH), mean age was 69 years and there was 1 (33%) woman. In the imatinib PAH group (n=5, 3.6% of all PAH), mean age was 49.6 years and there were 3 (60%) women. Conclusions Patients treated with TKIs, especially dasatinib, may develop PAH while the incidence of PAH with nilotinib and imatinib appears to be low. Further research is warranted to cover the gap of screening guidelines, which challenges the detection of CML patients treated with TKIs who develop PAH. As comparable outcomes are reported with first line therapy, in patients at risk for PAH, clinicians can opt for the therapy with decreased association with the syndrome.