Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network

Rafael Amorim Belo Nunes; Precil Diego Miranda de Menezes Neves; Leandro Menezes Alves da Costa; Philip Bachour; Marcelo José de Carvalho Cantarelli; Gustavo Bernardes de Figueiredo Oliveira; Álvaro Avezum Jr

doi:10.3389/fcvm.2023.888366

Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network

Front Cardiovasc Med. 2023 Feb 7:10:888366. doi: 10.3389/fcvm.2023.888366. eCollection 2023.

Authors

Rafael Amorim Belo Nunes¹, Precil Diego Miranda de Menezes Neves², Leandro Menezes Alves da Costa¹, Philip Bachour³, Marcelo José de Carvalho Cantarelli¹, Gustavo Bernardes de Figueiredo Oliveira², Álvaro Avezum Jr²

Affiliations

¹ Department of Cardiology, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
² International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.
³ Department of Hematology and Bone Marrow Transplant, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.

Abstract

Background: Breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs.

Objectives: This study aims to compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) < 50%, and venous thromboembolic events (VTE) in patients with CML treated with BCR-ABL TKIs, using data from a large multinational network.

Methods: Patients aged ≥ 18 years with CML treated with imatinib, dasatinib, or nilotinib without prior cardiovascular or cerebrovascular disease were included. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated.

Results: We identified 3,722 patients with CML under treatment with imatinib (n = 1,906), dasatinib (n = 1,269), and nilotinib (n = 547). Patients with imatinib compared to dasatinib showed a higher hazard ratio (HR) for ACE (HR 2,13, 95% CI 1.15-3.94, p = 0.016). Patients with imatinib presented a lower HR than nilotinib for ACE (HR 0.50, 95% CI 0.30-0.83, p = 0.0074). In relation to heart failure or LVEF < 50%, patients with imatinib had a higher HR than dasatinib (HR 9.41, 95% CI 1.22-72.17, p = 0.03), but no significant difference was observed between imatinib and nilotinib (HR 0.48, 95% CI 0.215-1.01, p = 0.064).

Conclusion: In this retrospective study with a large number of patients with CML, those treated with nilotinib had a higher 5-year ratio of ACE, while patients with dasatinib showed a lower ratio than patients with imatinib. The ratio of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.

Keywords: breakpoint cluster region-abelson (BCR-ABL); cardio-onco-hematology; cardiovascular safety; chronic myeloid leukemia; tyrosine kinase inhibitor (TKI).