P694Evaluation of preclinical atherosclerosis in chronic myeloid patients continuously treated with tyrosine kinase inhibitors
Authors: Shnalieva N , Zammoeva D , Chitanava T , Chiritso M , Boiarinova M , Vasilieva E , Lomaia E , Zaritskey A 
Published: October 2019

Abstract

In tyrosine kinase inhibitors (TKIs) era chronic myeloid leukemia (CML) became from fatal to well controlled chronic disease. Meanwhile it seems that some TKIs may have cardiovascular (CV) effects. The aim of the study was to assess signs of preclinical atherosclerosis (PA) on different TKIs in CML patients (pts).

Patients and method
In our study 126pts with CML obtained TKIs as any line at least 6mos were included. Males were 56 (44,5%). The median age was 52 (20–76)yrs. Pts with previous history of atherosclerotic CV events were excluded. There were 115 (91%), 61 (48%), 48 (38%), 12 (11%) pts ever obtained Imatinib (IMA), Nilotinib (NILO), Dasatinib (DASA) or Bosutinib (BOSU) with median treatment duration 22mos, 14mos, 16mos and 15,5mos, respectively. Median time since the first TKI was 48 mos. There are 79, 46, 12 pts obtained 2, 3 or 4 TKIs.
To assess PA ankle-brachial index (ABI) and intima media thickness (IMT) were measured. To evaluate ABI Vascular Screening System VaSera VS-1500 was used. Normal values for ABI and IMT were >0,9 and ≤1,1.

Results
ABI was abnormally low in 14/108 (13%) evaluable pts. Previous TKIs of IMA, NILO, DASA and BOSU were in 12 (86%) and 87 (93%), 9 (64%) and 41 (43%), 5 (35%) and 29 (31%), 1 (7%) and 9 (10%) pts with or w/t low ABI. All NILO its were pretreated with IMA. Only 2 pts previously obtained other TKIs. Median time on NILO was 23 mos and 15mos in pts with or w/t abnormal ABI, respectively. Median age for pts with or w/t low ABI was 53 and 52 yrs. The proportion of male pts were lower in abnormal vs normal ABI group – 29% and 44%. In NILO group 2 pts were male and median age for all pts was 51yrs.
IMT was evaluable in 86 pts. The median value of IMT was 0,8mm for all pts. It was abnormal in 12 (14%) pts with median thickness 1,3mm. All pts previously ever obtained IMA. NILO, DASA and BOSU were exposed in 5 (42%) and 33 (46%), 5 (42%) and 23 (31%), 1 (8%) and 7 (10%) pts with or w/t IMT abnormalities. The proportion of males was 4 (33%) and 34 (46%) among pts with or w/t abnormal IMT. Pts with high vs normal IMT were older with median age 64 vs 44yrs.
TKIs2 were ever obtained in 13/14 (93%) and 11/12 (92%)pts with abnormal ABI and IMT< respectively. Both ABI and IMT were abnormal only in 4 pts.
Heart SCORE was high and very high only in 18/80 (22,5%) pts. Median age for low vs high risk pts were much lower (40 vs 52yrs). There were no differences between treatment groups according to SCORE distribution.
Overall 9/50 (18%) and 3/32 (9%), 5/38 (13%) and 3/28 (11%)pts on NILO and DASA, had abnormal ABI and IMT.

Conclusion
CML pts heavily pretreated with different TKIs were included In the study. The most pts with abnormal ABI and IMT have ever been obtaining TKIs2. Pts with NILO more frequently experienced low ABI. There were not significant differences among TKIs groups regarding heart SCORE or IMT. It seems that extended PA is low on TKIs including NILO in CML pts w/t previous SVEs.

Acknowledgement/Funding
Funded from government assignment