Nilotinib (NIL) is approved for the first-line treatment of CML based
on the results of the ENESTnd study that demonstrated a higher efficacy
compared to imatinib (IM). However, there are concerns on the vascular
toxicity of NIL, disclosed by an increased rate of cardiovascular adverse
events (CVAEs) with respect to imatinib. For this reason, we investigated
the CVAEs in 2 studies of the GIMEMA CML WP that included NIL as
first-line treatment of CML: the GIMEMA CML 0307 trial (73 pts; NIL
400 mg BID), and the GIMEMA CML 0408 trial (123 pts; 3-months alternating
regime of NIL 400 mg BID and IM 400 mg QD). The median
age at CML diagnosis of all 196 pts was 55 (18-84) years; 59 (30%) pts
were ≥65 years; 52% were males; cardiovascular risk factors (CVRF: hypertension,
dyslipidemia, diabetes, BMI ≥30, and prior ischemic disease)
were present in 74 (38%) pts (median 1, range 1-4). There were no significant
differences between the pts characteristics in the 2 studies. The
median f-up was 61 months. Nineteen CVAEs occurred in 17 (8.6%) pts:
7 acute myocardial infarctions (MI); 5 PAODs; 2 carotid stenosis, 2 aortic
atherosclerosis, 1 stroke, 1 unstable angina, and 1 stable angina (1 patient
had 1 PAOD, 1 stroke, and 1 MI). In pts with CVAEs, the median age at
CML diagnosis was 67 (43-84 years), and the median interval from CML
diagnosis to CVAE was 38(1-76) months. Out of the 17 pts with CVAEs 53% were males; 70% were ≥65 years at CML diagnosis; 76% had at
least 1 CVRF, and 65% were treated with NIL alone. All pts but one
(who died at 90 years for congestive heart failure post MI) are alive.
Treatment of CVAEs included coronary angioplasty in 5 pts, lower limb
amputation in 2 pts, and peripheral vascular surgery in 2 pts; all other
pts received medical treatment; 12/17 pts permanently discontinued
NIL. In univariate analysis, the occurrence of CVAEs was associated with
age≥65 years (12/59[20%] vs 5/137[3.6%]; p=0.0004), the presence of at
least one CVRF (13/74[18%] vs 4/122[3.3%]; p=0.001), and the
monotherapy with NIL (11/73[15%] vs 6/123[4.8%]; p=0.018). CVAEs
occurred at a significant rate in pts treated with NIL-based regimes, and
in particularly in pts ≥65 years and/or with CVRF. Noteworthy, the alternating
schedule of NIL and IM resulted in a lower incidence of CVAEs
compared to NIL monotherapy. Thus, considering the morbidity associated
to CVAEs, the risk/benefit ratio of NIL monotherapy should be
carefully evaluated in selected groups of patients
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