Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs

Preetesh Jain, Hagop Kantarjian, Prajwal C. Boddu, Graciela M. Nogueras-González, Srdan Verstovsek, Guillermo Garcia-Manero, Gautam Borthakur, Koji Sasaki, Tapan M. Kadia, Princy Sam, Hycienth Ahaneku, Susan O’Brien, Zeev Estrov, Farhad Ravandi, Elias Jabbour, Jorge E. Cortes

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10 Scopus citations

Abstract

Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n 5 71) and 800 mg (n 5 203), nilotinib (n 5 108), dasatinib (n 5 106), and ponatinib (n 5 43). Characteristics and incidence of new-onset CV-AEs and AT-AEs were analyzed. Poisson regression models assessed factors associated with AE incidence. Median follow-up was 94 months (range, 2-195). Overall, 237 patients (45%) developed CV-AEs and 46 (9%) developed AT-AEs. Hypertension was the most common AE seen in 175 patients (33%; grade 3/4 in 17%). CV-AE and AT-AE incidence ratios (IRs) with 95% confidence intervals (CIs) were 8.6 (7.6-9.8) and 1.7 (1.2-2.2) per 100 person-years. Among the TKIs, ponatinib showed the highest IR (95% CI) for CV-AEs and AT-AEs at 40.7 (27.9-59.4) and 9.0 (4.1-20.1). In multivariate analysis, ponatinib therapy was associated with increased incidence rate ratio (IRR) for CV-AEs (4.62; 95% CI, 2.7-7.7; P, .0001) and AT-AEs (6.38; 95% CI, 1.8-21.8; P, .0001) compared with imatinib 400. In summary, there is an increased risk of CV-AEs (except hypertension) and AT-AEs in CML patients treated with newer TKIs, particularly with ponatinib. Patients on TKIs must be informed and closely monitored for vascular AEs. These studies were registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, #NCT00050531, #NCT00254423, #NCT00129740, and #NCT01570868.

Original languageEnglish (US)
Pages (from-to)851-861
Number of pages11
JournalBlood Advances
Volume3
Issue number6
DOIs
StatePublished - Mar 26 2019
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Jain, P., Kantarjian, H., Boddu, P. C., Nogueras-González, G. M., Verstovsek, S., Garcia-Manero, G., Borthakur, G., Sasaki, K., Kadia, T. M., Sam, P., Ahaneku, H., O’Brien, S., Estrov, Z., Ravandi, F., Jabbour, E., & Cortes, J. E. (2019). Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Advances, 3(6), 851-861. https://doi.org/10.1182/bloodadvances.2018025874