Abstract
Tyrosine kinase inhibitors (TKI) may offer a normal life expectancy to Chronic Myeloid Leukemia (CML) patients. However, a higher than expected incidence of arterial occlusive events (AOEs) was observed during treatment with nilotinib. We previously showed an “inflammatory status” during nilotinib that may explain the increased incidence of AOEs. Thus, we conducted this prospective KIARO study involving 186 CML patients (89 imatinib, 59 nilotinib, 38 dasatinib). Interleukin 6 (IL6), interleukin 10 (IL10), Tumor Necrosis Factor-α (TNFα), oxLDL, and high-sensitivity C-reactive protein (hs-CRP) plasma levels were measured at diagnosis and during treatment, with the aim to investigate changes in the inflammatory status favoring AOEs of each patient. Clinical and biochemical pro-atherothrombotic profiles and the 10-year SCORE chart were also evaluated. We showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib, as demonstrated by higher hs-CRP and oxLDL levels and increased IL6/IL10 and TNFα/IL10 ratios only in nilotinib cohort. After median follow-up of 23.3 months starting from TKI, 10/186 patients (5.4%) suffered an AOE. Approximately 5/10 (50%) AOEs occurred during nilotinib treatment despite a lower 10-year SCORE and a lower median age in this subgroup. A longer follow-up is needed to further confirm the active role of nilotinib in AOEs pathogenesis.
Highlights
The great success of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) marked a decisive change in the history of the disease, offering patients a life expectancy comparable to that of the general population [1]
The KIARO study represents the first prospective real life study in CP-Chronic Myeloid Leukemia (CML) patients demonstrating the occurrence of a proinflammatory and pro-oxidative status during nilotinib treatment when compared with imatinib and dasatinib
The latter evidence could play a crucial role in the pathogenesis of the arterial occlusive events (AOEs) observed more frequently in CML patients receiving nilotinib
Summary
The great success of tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) marked a decisive change in the history of the disease, offering patients a life expectancy comparable to that of the general population [1]. And more recent reports underlined the increased rate of vascular adverse effects, often arterial occlusive, in newly diagnosed CML patients treated with TKIs [4,5,6]. Nilotinib, unlike imatinib, was confirmed to be followed by a significant rate of cardiovascular (CV) adverse effects, namely, ischemic ones, which were found to increase with long-lasting treatment exposure [7, 8]. The use of the Systematic Coronary Risk Evaluation (SCORE) chart (a tool for cardiovascular risk stratification proposed by the European Society of Cardiology) was suggested to estimate the risk of developing AOEs in patients treated with nilotinib [12, 13]. Low plasma levels of low-density lipoprotein cholesterol (LDL-cholesterol) were associated with a significant lower risk of AOEs in CML patients treated with nilotinib [16]
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