Change of right ventricular systolic pressure can indicate dasatinib-induced pulmonary arterial hypertension in chronic myeloid leukemia

Cancer Med. 2021 Mar;10(5):1515-1524. doi: 10.1002/cam4.3588. Epub 2021 Feb 15.

Abstract

Background: We investigated the feasibility of the clinical application of non-invasive transthoracic echocardiography for diagnosis of pulmonary arterial hypertension induced by dasatinib (D-PAH) in chronic myeloid leukemia (CML).

Methods: A total of 451 CML patients who were examined by 2D-echocardiography at least once at baseline and/or during dasatinib therapy as frontline (n = 196) and subsequent line (n = 255) therapies were included in this study. D-PAH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg with relevant symptoms and the absence of other specific etiologies.

Results: A total of 847 echocardiographies were performed including at baseline (n = 255) and during dasatinib treatment (n = 592). During the median of 36.2 (0.1-181.8) months of dasatinib therapy, the level of RVSP gradually increased (Spearman's r = 0.2819, p < 0.001) and the mean RVSP was significantly increased after taking dasatinib therapy compared with baseline. During dasatinib therapy, 56 (12.4%) patients had RVSP >40 mm Hg without (asymptomatic, n = 27, 48.2%) or with symptoms (D-PAH, n = 29, 51.8%). All asymptomatic patients maintained dasatinib therapy without further symptoms and the D-PAH patients ultimately switched to other tyrosine kinase inhibitors. After dasatinib discontinuation, 13 (45%) and 15 (52%) patients showed RVSP normalization and gradual decrease, respectively.

Conclusions: Our large cohort study demonstrated that the gradual increment of RVSP might be induced by dasatinib and non-invasive echocardiography can be fast way for early diagnosis as well as for monitoring of D-PAH.

Keywords: chronic myeloid leukemia; dasatinib; echocardiography; pulmonary arterial hypertension; right ventricular systolic pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Dasatinib / adverse effects*
  • Drug Substitution
  • Echocardiography / methods
  • Echocardiography / statistics & numerical data
  • Feasibility Studies
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pulmonary Arterial Hypertension / chemically induced*
  • Pulmonary Arterial Hypertension / diagnostic imaging
  • Systole / physiology
  • Ventricular Function, Right / drug effects*
  • Ventricular Function, Right / physiology

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Dasatinib