Journal of Vascular Medicine & Surgery

Is Nilotinib Therapy at Risk of Unstable Atheroma?

El Harake Sarah¹, Charbonnier Aude² and Sarlon-Bartoli Gabrielle^{1* 1}Department of Vascular Medicine, Assistance Publique Hôpitaux de Marseille- Hôpital de la Timone, Aix-Marseille University, 264, Rue Saint-Pierre, 13385 Marseille Cedex 05, France
²Institute Paoli-Calmettes, département d'Onco- hématologie, 232, Boulevard Sainte-Marguerite, BP 156, 13273 Marseille Cedex 9, France
^*Correspondence: Sarlon-Bartoli Gabrielle, Department of Vascular Medicine, Assistance Publique Hôpitaux de Marseille- Hôpital de la Timone, Aix-Marseille University, 264, Rue Saint-Pierre, 13385 Marseille Cedex 05, France, Email:

Received: 14-Sep-2021 Published: 05-Oct-2021

Description

Second and third generation tyrosine kinase inhibitors like nilotinib have been validated in daily practice for the treatment of Chronic Myeloid Leukaemia (CML). We described recently for the first-time the aspect of arterial ultrasound lesion of CML patients during nilotinib therapy [1]. We demonstrated in this short cohort of 74 patients that 33.8% of patients had ultrasound arterial anomalies when they systematically screened by a vascular specialist. This result are in phase of few studies suggested a higher prevalence of Peripheral Arterial Disease (PAD) during this therapy almost 30% [2-8]. Even if no significant vascular adverse events had been reported in initial clinical trials (<1%) [9,10]. In our work the most involved territory was the carotid bulb for 44% of the affected patients like in the Figure 1. 88% of the arterial ultrasound anomalies were plaques, 44%>50% stenosis and 12% occlusion. 72.7% of the plaques were echolucent or hypoechogenic. In fact with ultrasound imaging different atheroma anomalies can be described: plaque and its echogenicity, stenosis or occlusion. The aspect of arterial ultrasound lesion is very important particularly the grayscale (echogenicity). Echolucent or hypoechogenic plaques are associated with unstable atheroma because it reflects lipid core of atheroma with thin fibrous cap [11]. In literature, the carotid plaques with low grayscale median were associated with a twofold increase in stroke [12,13]. These echolucent lesions are sometimes difficult to detect during ultrasonography because echogenicity is similar to the circulating blood. This ultrasound aspect may be secondary to the increase in blood lipids sometimes induced by nilotinib [14]. Also in our study, patients with clinical and/or ultrasound arterial anomalies at baseline were significantly older (64.9 vs. 49.3 P<0.001), older at nilotinib initiation (60.8 vs 46.5 P<0.001), with more arterial hypertension (40% vs. 12.2% P=0.01), with more cardiovascular risk factors (P=0.03). These results are closed from literature that underlying predisposing factors of vascular adverse events with nilotinib therapy: High doses, long exposure to nilotinib and pre-existing cardiovascular risk factors [8,15]. To response at this adverse event in 2016 the France Intergroupe des Leucémies Myeloides Chroniques proposed practical recommendations to minimize the risk and the severity of cardiovascular events in nilotinibtreated patients [16]. Thus a moderate SCORE risk encourages screening arteries including carotid and leg arteries with duplex ultrasound. In these recommendations a low SCORE risk patient should not be systematically detected by ultrasound however in our cohort, in patient with no cardiovascular risk factor, 12.5% had vascular anomalies (n=24). It was closed from others data: Some PAD occurred in younger patients without risks factors [17]. Ultrasonography is a widely painless accessible method to detect arterial anomalies, less expensive than other examinations. In conclusion, treatment with nilotinib seems to be associated to atherosclerosis. The prevalence of ultrasound arterial anomalies is high, especially with longue nilotinib exposure, in older patients and in the presence of several cardiovascular risk factors. Ultrasound characteristics are high frequency of echolucent plaques which reflect unstable atheroma. We believe that the initiation of nilotinib therapy should systematically be associated with a cardiovascular evaluation in all patients, even in the absence of cardiovascular risk factors. We also believe in the importance of close vascular follow-up in these patients and regular monitoring of the biological lipid profile of these patients.

Figure 1: Example of bilateral echolucent carotid plaque. A right carotid bulb; B left carotid bulb. 39 years men without cardiovascular risk factors, CML since 5 years, nilotinib during 4 years, cholesterol LDL 1.5 g/l.

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