BACKGROUND: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. OBJECTIVE: To investigate the incidence of vascular events in patients with CML treated with first- and second-generation TKIs. DESIGN: Retrospective cohort study using nationwide population-based registries. SETTING: Sweden. PATIENTS: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. MEASUREMENTS: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. RESULTS: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. LIMITATIONS: Patients may have been exposed to multiple TKIs. Data on second- and third-generation TKIs were limited. CONCLUSION: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs. PRIMARY FUNDING SOURCE: No external funding.
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. OBJECTIVE: To investigate the incidence of vascular events in patients with CML treated with first- and second-generation TKIs. DESIGN: Retrospective cohort study using nationwide population-based registries. SETTING: Sweden. PATIENTS: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. MEASUREMENTS: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. RESULTS: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. LIMITATIONS: Patients may have been exposed to multiple TKIs. Data on second- and third-generation TKIs were limited. CONCLUSION: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs. PRIMARY FUNDING SOURCE: No external funding.
Authors: Koji Sasaki; Hagop M Kantarjian; Susan O'Brien; Farhad Ravandi; Marina Konopleva; Gautam Borthakur; Guillermo Garcia-Manero; William G Wierda; Naval Daver; Alessandra Ferrajoli; Koichi Takahashi; Preetesh Jain; Mary Beth Rios; Sherry A Pierce; Elias J Jabbour; Jorge E Cortes Journal: Int J Hematol Date: 2019-03-04 Impact factor: 2.490
Authors: Peter Valent; Emir Hadzijusufovic; Gregor Hoermann; Wolfgang Füreder; Gerit-Holger Schernthaner; Wolfgang R Sperr; Rudolf Kirchmair; Dominik Wolf Journal: Leuk Res Date: 2017-05-12 Impact factor: 3.156
Authors: Umberto Campia; Javid J Moslehi; Laleh Amiri-Kordestani; Ana Barac; Joshua A Beckman; David D Chism; Paul Cohen; John D Groarke; Joerg Herrmann; Carolyn M Reilly; Neal L Weintraub Journal: Circulation Date: 2019-03-26 Impact factor: 29.690
Authors: Ching-Jen Chen; Brian J Sorace; Aria Shakeri; Min S Park; Andrew M Southerland; Bradford B Worrall; M Yashar S Kalani Journal: BMJ Case Rep Date: 2018-04-03