TY - JOUR
T1 - Nilotinib-associated vascular events
AU - Quintás-Cardama, Alfonso
AU - Kantarjian, Hagop
AU - Cortes, Jorge
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/10
Y1 - 2012/10
N2 - Nilotinib is a highly selective inhibitor of the inactive conformation of ABL1 kinase. An improved topologic fit to the ABL1 protein-binding surface contributes to its increased potency over imatinib. This higher selectivity in vitro translated to an improved tolerability in vivo. In fact, nilotinib therapy in the frontline phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study was associated with an improved toxicity profile compared with that of imatinib. Intriguingly, several cases of severe peripheral artery occlusive disease (PAOD) have been reported among patients treated with nilotinib in small series. We have identified 5 patients with chronic myeloid leukemia (CML) in whom vascular events developed that were likely related to nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular accidents, and 3 other patients had PAOD (2 of them with other vascular events, including coronary artery disease and pulmonary emboli, respectively). Risk factors for vascular disease were present in only 1 patient with a history of diabetes mellitus. Although the incidence of vascular events is low, this potential complication should be taken into account when selecting nilotinib for the treatment of CML.
AB - Nilotinib is a highly selective inhibitor of the inactive conformation of ABL1 kinase. An improved topologic fit to the ABL1 protein-binding surface contributes to its increased potency over imatinib. This higher selectivity in vitro translated to an improved tolerability in vivo. In fact, nilotinib therapy in the frontline phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study was associated with an improved toxicity profile compared with that of imatinib. Intriguingly, several cases of severe peripheral artery occlusive disease (PAOD) have been reported among patients treated with nilotinib in small series. We have identified 5 patients with chronic myeloid leukemia (CML) in whom vascular events developed that were likely related to nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular accidents, and 3 other patients had PAOD (2 of them with other vascular events, including coronary artery disease and pulmonary emboli, respectively). Risk factors for vascular disease were present in only 1 patient with a history of diabetes mellitus. Although the incidence of vascular events is low, this potential complication should be taken into account when selecting nilotinib for the treatment of CML.
KW - BCR-ABL1
KW - Chronic myeloid leukemia
KW - Nilotinib
KW - Vascular events
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U2 - 10.1016/j.clml.2012.04.005
DO - 10.1016/j.clml.2012.04.005
M3 - Article
C2 - 22633167
AN - SCOPUS:84867427628
VL - 12
SP - 337
EP - 340
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2650
IS - 5
ER -