Analysis of Arterial Occlusive Events (AOE) in CML Patients Using Real-World Data : A Large Cohort

Background

While the prognosis of chronic myeloid leukemia (CML) has been significantly improved by the development of tyrosine kinase inhibitors (TKIs), the importance of managing various adverse events associated with long-term TKI treatment is increasing. In particular, arterial occlusive events (AOEs) can be fatal and potentially cause irreversible sequelae in patients, requiring the choice of TKIs according to individual patient risk and proactive therapeutic interventions for prevention. In this study, we conducted an analysis using data from the DPC database, MDV (Medical Data Vision Co., Ltd., and examined AOE in the real-world setting of a large cohort.

Methods

We extracted data from MDV for 2,113 patients aged 18-100 (average age 61.3; 1,326 men and 787 women) who were diagnosed with CML and received TKI treatment from Jan 2017 to Dec 2020. We used logistic regression analysis to analyze the frequency and timing of AOE, and individual AOE risk factors such as gender, age, and history of cardiovascular event, hypertension, diabetes, and dyslipidemia, by various TKI treatment lines.

Results

Of the 2,113 MDV registrants, 1,381 were 1st-line TKI treatment patients, 550 were 2nd-line, 150 were 3rd-line, and 32 were 4th-line or later. The incidence of AOE by treatment line was increasing with the later treatment lines (8.5% for 1st-line, 12.5% for 2nd, and 14.7% for 3rd: p=0.0079 (1st vs 2nd), p=0.0164 (1st vs 3rd)). The person-year method (/1000 person-years) was 37.7 for 1st-line, 95.1 for 2nd-line, and 143.9 for 3rd-line. The median time to AOE onset was 27.0 days for 1st-line, 25.0 days for 2nd-line, and 25.5 days for 3rd-line. Furthermore, analyzed by type of AOEs, we found that the median time of stroke and peripheral arterial occlusive disease were similar regardless of the treatment line. However, incident rate of myocardial infarction was increased at later line (26.0 days for 1st-line, 29.0 days for 2nd-line, and 45.0 days for 3rd-line).

In the analysis of AOE risk factors, all factors showed significant differences in the comparison between 1st-line and 2nd-line in univariate analysis, but in multivariate analysis, age, gender, dyslipidemia, and hypertension were significant risk factors in 1st-line, while age and hypertension were significant in 2nd-line. On the other hand, hypertension, diabetes, and dyslipidemia were significant in univariate analysis, and diabetes was significant in multivariate analysis in 3rd-line group.

【Conclusion】The results of the real-world data analysis of a large cohort using the DPC database showed that the incidence of AOE increased with the estimation of treatment lines, and significant risk factors varied in each treatment line. In particular, hypertension and diabetes were significant risk factors for AOE in all treatment lines in both univariate and multivariate analyses, suggesting that the proactive therapeutic interventions are strongly recommended for these risk factors.

Takaku:Sysmex: Research Funding; ThinkCite: Research Funding; Phizer: Honoraria; Novartis: Honoraria; Otsuka: Honoraria, Research Funding. Kojima:Otsuka Pharmaceutical Co., Ltd.: Current Employment. Yanai:Otsuka Pharmaceutical Co., Ltd.: Current Employment.