Abstract
ENESTnd trial, nilotinib showed superior efficacy and good tolerability compared with standard dose of imatinib in chronic phase chronic myeloid leukemia (CP CML). However, serious vascular adverse events such as ischemic heart disease (IHD) and peripheral arterial occlusive disease (PAOD) have been reported. Therefore, we have prospectively evaluated for emergence of PAOD in all (CML patients treated with nilotinib.
Between May 2005 and April 2013, a total of 98 CP CML patients on nilotinib treatment were tested with laboratory studies, electrocardiography and ankle brachial index (ABI) + pulse wave velocity (PWV). Abnormal ABI index was defined with below 1.0 and abnormal PWV as over 1200∼2000 cm/sec adjusted by age. and patients who had abnormal ABI or PWV were performed with computed tomography angiography.
So far, 88 of total 98 patients (57 male) were evaluated with screening test. 17 patients of 88 showed abnormal ABI or PWV. Finally, 3 patients (3.4%) of 17 were diagnosed with overt PAOD by CT angiography (2 upper extremity, 1 lower extremity). The median age was 46 year old (range, 19∼72). The median duration of disease was 49 months (range,1.2 ∼ 65) and 51.3 months (range,36 ∼ 115) in the patients treated with first-line and second-line nilotinib, respectively. The median mean daily dosage of nilotinib was 710mg (range, 656∼800mg) and 737 mg (range, 500∼800mg) in each group. The duration of nilotinib treatment was 46.3 months (range, 0.7∼64.2) and 25.0 months (range, 2.8∼55.8) in each group. Comparing first and second-line nilotinib treated patients, an abnormal ABI or PWV (1 versus 16 patients) and overt PAOD (0 versus 3 patients) was more frequent in patients with second-line nilotinib (p=0.042, p< 0.001, p<0.001).
Our preliminary data suggest an importance of PAOD evaluation in patients with long-term nilotinib treatment (p=0.042) and a routine assessment of PAOD including ischemic heart disease (IHD) is strongly recommended on regular basis.
| Parameters . | All . | 1st line nilotinib . | 2nd line nilotinib . |
|---|---|---|---|
| n | 98 | 53 | 45 |
| Clinical risk factors for PAOD in patients under nilotinib | |||
| Male (%) | 63 (35%) | 35 (66%) | 62 (31%) |
| Median age (range) | 45 (16∼82) | 44 (22∼72) | 46 (16∼82) |
| History of smoking (%) | 22 (29%) | 18 (25%) | 27 (31%) |
| Hypertension (%) | 29 (29.5%) | 13 (25%) | 16 (36%) |
| Coronary heart disease(%) | 0 | 0 | 0 |
| Diabetes mellitus (%) | 7(6%) | 3 (6%) | 4 (9%) |
| Median BMI (range) | 23 (18.1∼30.5) | 20 (18.1∼21.8) | 25 (21.0∼30.5) |
| Screening chemistry data for PAOD in patients under nilotinib | |||
| Median Fasting blood sugar (mg/dL) | 114(85∼155) | 120 (103∼155) | 110 (85∼150) |
| Median total cholesterol (mg/dL) | 213 (40∼220) | 195 (174∼220) | 221 (40∼157) |
| Median triglyceride (mg/dL) | 104 (46∼157) | 83 (46∼116) | 112 (40∼157) |
| CML-associated baseline characteristics before screening for PAOD (17 patients) | |||
| Median duration of CML(months,range) | 51.2 (1.2∼117) | 46 (1.2∼63) | 53.3 (36∼117) |
| Median daily mean dose (mg, range) | 730 (500∼800) | 710 (656∼800) | 737 (500∼800) |
| Duration of nilotinib treatment (month, range) | 31 (0.7∼64.2) | 46.3 (0.7∼64.2) | 25.0(2.8∼55.8) |
| Results | |||
| Pathological ABI(%):<0.9 | 1/17 (6%) | 0 (0%) | 1 (8%) |
| Pathological Arterial stiffness (%) (> 1200∼2000 cm/sec adjusted by age) | 8/17 (47%) | 1/4 (25%) | 7/13 (54%) |
| Parameters . | All . | 1st line nilotinib . | 2nd line nilotinib . |
|---|---|---|---|
| n | 98 | 53 | 45 |
| Clinical risk factors for PAOD in patients under nilotinib | |||
| Male (%) | 63 (35%) | 35 (66%) | 62 (31%) |
| Median age (range) | 45 (16∼82) | 44 (22∼72) | 46 (16∼82) |
| History of smoking (%) | 22 (29%) | 18 (25%) | 27 (31%) |
| Hypertension (%) | 29 (29.5%) | 13 (25%) | 16 (36%) |
| Coronary heart disease(%) | 0 | 0 | 0 |
| Diabetes mellitus (%) | 7(6%) | 3 (6%) | 4 (9%) |
| Median BMI (range) | 23 (18.1∼30.5) | 20 (18.1∼21.8) | 25 (21.0∼30.5) |
| Screening chemistry data for PAOD in patients under nilotinib | |||
| Median Fasting blood sugar (mg/dL) | 114(85∼155) | 120 (103∼155) | 110 (85∼150) |
| Median total cholesterol (mg/dL) | 213 (40∼220) | 195 (174∼220) | 221 (40∼157) |
| Median triglyceride (mg/dL) | 104 (46∼157) | 83 (46∼116) | 112 (40∼157) |
| CML-associated baseline characteristics before screening for PAOD (17 patients) | |||
| Median duration of CML(months,range) | 51.2 (1.2∼117) | 46 (1.2∼63) | 53.3 (36∼117) |
| Median daily mean dose (mg, range) | 730 (500∼800) | 710 (656∼800) | 737 (500∼800) |
| Duration of nilotinib treatment (month, range) | 31 (0.7∼64.2) | 46.3 (0.7∼64.2) | 25.0(2.8∼55.8) |
| Results | |||
| Pathological ABI(%):<0.9 | 1/17 (6%) | 0 (0%) | 1 (8%) |
| Pathological Arterial stiffness (%) (> 1200∼2000 cm/sec adjusted by age) | 8/17 (47%) | 1/4 (25%) | 7/13 (54%) |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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