ANALYSIS OF VASCULAR ADVERSE EVENTS IN TKI TREATED JAPANESE CML PATIENTS: RETROSPECTIVE LARGE COHORT STUDY OF CML COOPERATIVE STUDY GROUP
Author(s): ,
Isao Fujioka
Affiliations:
Department of Hematology,Juntendo University School of Medicine,Tokyo,Japan
,
Tomoiku Takaku
Affiliations:
Department of Hematology,Juntendo University School of Medicine,Tokyo,Japan
,
Noriyoshi Iriyama
Affiliations:
Division of Hematology and Rheumatology, Department of Medicine,Nihon University School of Medicine,Tokyo,Japan
,
Michihide Tokuhira
Affiliations:
Department of Hematology,Saitama Medical Center, Saitama Medical University,Saitama,Japan
,
Eriko Sato
Affiliations:
Division of Hematology, Department of Medicine,Juntendo University Nerima Hospital,Tokyo,Japan
,
Maho Ishikawa
Affiliations:
Department of Hemato-Oncology,Comprehensive Cancer Center, Saitama Medical University International Medical Center,Saitama,Japan
,
Tomonori Nakazato
Affiliations:
Department of Hematology,Yokohama Municipal Citizen's Hospital,Yokohama,Japan
,
Kei-Ji Sugimoto
Affiliations:
Department of Hematology,Juntendo University Urayasu Hospital,Urayasu,Japan
,
Hiroyuki Fujita
Affiliations:
Department of Hematology,Saiseikai Yokohama Nanbu Hospital,Yokohama,Japan
,
Norio Asou
Affiliations:
Department of Hemato-Oncology,Comprehensive Cancer Center, Saitama Medical University International Medical Center,Saitama,Japan
,
Masahiro Kizaki
Affiliations:
Department of Hematology,Saitama Medical Center, Saitama Medical University,Saitama,Japan
,
Yoshihiro Hatta
Affiliations:
Division of Hematology and Rheumatology, Department of Medicine,Nihon University School of Medicine,Tokyo,Japan
,
Norio Komatsu
Affiliations:
Department of Hematology,Juntendo University School of Medicine,Tokyo,Japan
Tatsuya Kawaguchi
Affiliations:
Department of Hematology and Infectious Diseases,Kumamoto University Hospital,Kumamoto,Japan
EHA Library. Fujioka I. May 18, 2017; 180834; E1058
Isao Fujioka
Isao Fujioka
Contributions
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Abstract

Abstract: E1058

Type: Eposter Presentation

Background
Chronic myeloid leukemia (CML) is a disease of hematopoietic stem cells resulting from oncogenic chromosome translocation that leads to the formation of the BCR-ABL1 fusion gene. Treatment of chronic phase (CP) CML has dramatically changed since the emergence of the first-in class tyrosine kinase inhibitor (TKI) imatinib, and treatment based on TKI has improved the outcome in the majority of CP-CML patients. Nowadays, second generation TKIs are available and brought about faster and deeper clinical responses, and lower disease progression rate than imatinib. On the other hand, longer treatment duration and the increased types of TKIs gave rise to various kinds of unexpected adverse events (AEs). In 2011, drug-induced peripheral artery occlusive disease (PAOD) was first reported, followed by vascular AEs (VAEs) including ischemic heart disease (IHD) and cerebral infarction (CI). Furthermore, it became clear that the incidence of VAEs increased with the dose and treatment duration, therefore VAEs are considered a more fatal complication of TKI treatment. However, there is no available data about the incidence of VAEs in Japanese patients.

Aims
We investigated the vascular safety issue and estimated the 1000 person-years risk of developing VAEs during TKI treatment, including imatinib, nilotinib, and dasatinib, using 3 risk assessment tools among 320 Japanese patients who were enrolled in the CML Cooperative Study Group.

Methods
A surveillance data of 320 patients enrolled in the CML Cooperative Study Group was conducted in this analysis. Briefly, the study included patients who were diagnosed with CML-CP from April 2001 to January 2016, whose median age was 57 years old (15-80) and median time of follow up was 64.2 months. Patients in the accelerated or blastic phase (AP/BP) were excluded. The study was approved by the research ethics boards of each institutions and was conducted in accordance with the Declaration of Helsinki.

All patients who developed VAEs were analyzed using 3 risk assessment tools (SCORE chart, Framingham risk score, Suita-score) to estimate the patients’ 10-year risk of VAEs.

Results
Among the 320 newly diagnosed CML-CP patients, 16 (5.0%) cases of VAEs were reported during the study period. Seven cases were treated by imatinib, 3 cases by nilotinib, 1 case by dasatinib, 4 cases were a switch from imatinib to nilotinib, and 1 case was a switch from dasatinib to nilotinib. The VAEs were 9 IHD, 5 CI, and 2 PAOD cases. Results from the 3 risk assessment tools are as follows: SCORE (2 low, 9 moderate, 1 high, 4 very high risk), Framingham score (3 low, 5 moderate, 7 high risk), and Suita-score (13 low, 1 intermediate, 1 high risk). The incidence rate of IHD and CI per 1000 person-years were 5.26 and 2.92 in the enrolled CML-CP patients, 4.65 and 2.33 in the imatinib-treated patients, 14.34 and 10.75 in the nilotinib-treated patients, 4.08 and no case in the dasatinib-treated patients, and 1.787 and 3.342 in the age-matched general population, respectively

Among the 320 newly diagnosed CML-CP patients, 16 (5.0%) cases of VAEs were reported during the study period. Seven cases were treated by imatinib, 3 cases by nilotinib, 1 case by dasatinib, 4 cases were a switch from imatinib to nilotinib, and 1 case was a switch from dasatinib to nilotinib. The VAEs were 9 IHD, 5 CI, and 2 PAOD cases. Results from the 3 risk assessment tools are as follows: SCORE (2 low, 9 moderate, 1 high, 4 very high risk), Framingham score (3 low, 5 moderate, 7 high risk), and Suita-score (13 low, 1 intermediate, 1 high risk). The incidence rate of IHD and CI per 1000 person-years were 5.26 and 2.92 in the enrolled CML-CP patients, 4.65 and 2.33 in the imatinib-treated patients, 14.34 and 10.75 in the nilotinib-treated patients, 4.08 and no case in the dasatinib-treated patients, and 1.787 and 3.342 in the age-matched general population, respectively.

Conclusion
The incidence rate of IHD per 1000 person-years were higher in the nilotinib- and lower in imatinib- and dasatinib-treated CML patients, and the patients showed almost the same rate of CI as compared with the age-matched general population, even though the incidence of VAEs were lower in Japanese as compared to the European cohort. More patients were estimated to have very-high and high risk of VAEs in the SCORE and Framingham risk score assessment tools as compared with the Suita-score tool.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Tyrosine kinase inhibitor, Thromboembolic events, Chronic myeloid leukemia

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