Evaluation of Comorbidities Relevant to Tyrosine Kinase Inhibitor Treatment Among Patients with Chronic Myelogenous Leukemia in the U.S. Managed Care Setting
Authors: Jabbour Elias , Makenbaeva Dinara , Lingohr-Smith Melissa , Lin Jay 
Published: October 2019

Abstract
Introduction: Three BCR-ABL tyrosine kinase inhibitors (TKIs), imatinib, dasatinib and nilotinib, have been FDA approved as first-line chronic myelogenous leukemia (CML) treatments and are considered by the National Comprehensive Cancer Network (NCCN) guidelines as category 1 recommendation. NCCN treatment guidelines note that based on toxicity profiles of 2nd generation TKIs, certain comorbidities should be taken into consideration when selecting appropriate care for patients as one TKI may be recommended over another for a particular CML patient. In this regard the NCCN guidelines state that nilotinib may be more appropriate for CML patients with a history of lung disease or who are at risk for pleural effusions, while dasatinib may be more appropriate for those with a history of arrhythmias, heart disease, pancreatitis, or hyperglycemia. The prevalence of these comorbidities is not well described in the literature. Therefore, the primary objective of this study was to assess the prevalence of the relevant comorbidities among CML patients prior to initiation of treatment with a TKI in the U.S. managed care setting.
Methods: Patient data were extracted from the Truven Health Analytics Commercial and Medicare MarketScan® Research databases between 1/1/2006 and 06/30/2013. The study population was comprised of adult patients with CML newly initiated on a TKI treatment (imatinib, dasatinib, or nilotinib). The first TKI prescription was defined as the index event. Patients were required to have at least 12 months of continuous data prior to the index event, defined as the baseline period. Age, gender, region, and health plan type were evaluated in the baseline period. The prevalence of comorbidities mentioned in the NCCN guidelines (heart disease, arrhythmia, diabetes, pancreatitis, pleural effusion, and lung disease) was assessed in the baseline period based on at least two corresponding claims to identify a recurrent or chronic condition.
Results: The median age of the study population (n=2,296) was 56 years, with 77% (1,766) being <65 years of age. Fifty-seven percent were male. The majority of the study population (59%) had health plans offered by preferred provider organizations (PPO). Of the study population 38% were from the South, 30% were from the North Central region of the U.S., 16% were from the West, and 14% were from the Northeast. Approximately 41% of the study population had at least one comorbidity mentioned in the NCCN guidelines (Table). The most prevalent comorbidity was heart disease, followed by diabetes, and lung disease.
Conclusions: Prevalence of comorbidities relevant to TKI treatment choices for CML patients is substantial. These comorbidities should be taken into consideration when selecting appropriate care for patients as one TKI may confer a better safety profile for one patient over another. Open access to TKIs in a managed care setting may be important in order to enable physicians to choose the most appropriate TKI treatment for a CML patient according to NCCN guidelines.
Table. Prevalence of Comorbidities Among the CML Study Population Condition N % Heart Disease 523 22.8 Arrhythmia 152 6.6 Diabetes 409 17.8 Pancreatitis 8 0.4 Pleural Effusion 47 2.1 Lung Disease 292 12.7 Any of the Above Conditions 937 40.8

Disclosures
Jabbour: Ariad, Novartis, BMS, Pfizer, and Teva : Consultancy. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Lingohr-Smith:Bristol-Myers Squibb: Consultancy, Research Funding. Lin:Bristol-Myers Squibb: Consultancy, Research Funding.