TY - JOUR
T1 - Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs
AU - Jain, Preetesh
AU - Kantarjian, Hagop
AU - Boddu, Prajwal C.
AU - Nogueras-González, Graciela M.
AU - Verstovsek, Srdan
AU - Garcia-Manero, Guillermo
AU - Borthakur, Gautam
AU - Sasaki, Koji
AU - Kadia, Tapan M.
AU - Sam, Princy
AU - Ahaneku, Hycienth
AU - O’Brien, Susan
AU - Estrov, Zeev
AU - Ravandi, Farhad
AU - Jabbour, Elias
AU - Cortes, Jorge E.
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/3/26
Y1 - 2019/3/26
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2018025874
DO - 10.1182/bloodadvances.2018025874
M3 - Article
C2 - 30885996
AN - SCOPUS:85068052535
SN - 2473-9529
VL - 3
SP - 851
EP - 861
JO - Blood Advances
JF - Blood Advances
IS - 6
ER -