title: Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis.
abstract: Peripheral arterial occlusive disease (PAOD) occurs in patients with chronic phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs). The risk of developing PAOD on TKI therapy is unknown and causality has not been established. Patients with CML-CP from three randomized phase III studies (IRIS, TOPS and ENESTnd) were divided into three cohorts: no TKI (cohort 1; n=533), nilotinib (cohort 2; n=556) and imatinib (cohort 3; n=1301). Patients with atherosclerotic risk factors were not excluded. Data were queried for terms indicative of PAOD. Overall, 3, 7 and 2 patients in cohorts 1, 2 and 3, respectively, had PAOD; 11/12 patients had baseline PAOD risk factors. Compared with that of cohort 1, exposure-adjusted risks of PAOD for cohorts 2 and 3 were 0.9 (95% CI, 0.2-3.3) and 0.1 (95% CI, 0.0-0.5), respectively. Multivariate logistic regression revealed that nilotinib had no impact on PAOD rates compared with no TKI, whereas imatinib had decreased rates of PAOD compared with no TKI. Nilotinib was associated with higher rates of PAOD versus imatinib. Baseline assessments, preferably within clinical studies, of PAOD and associated risk factors should occur when initiating TKI therapy in CML; patients should receive monitoring and treatment according to the standard of care for these comorbidities.
authors: HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland. frankgiles@aol.com
authors: F J
authors: FJ
authors: Giles
authors: M J
authors: MJ
authors: Mauro
authors: F
authors: F
authors: Hong
authors: C-E
authors: CE
authors: Ortmann
authors: C
authors: C
authors: McNeill
authors: R C
authors: RC
authors: Woodman
authors: A
authors: A
authors: Hochhaus
authors: P D
authors: PD
authors: le Coutre
authors: G
authors: G
authors: Saglio
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001549:Benzamides / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000150:complications*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib