Incidence of type 2 diabetes mellitus and hyperlipidemia in patients prescribed dasatinib or nilotinib as first- or second-line therapy for chronic myelogenous leukemia in the US

Franklin, Meg; Burns, Leah; Perez, Samuel; Yerragolam, Deepak; Makenbaeva, Dinara

doi:10.1080/03007995.2017.1399870

Cited by 25 publications

(21 citation statements)

References 13 publications

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“…Hypercholesterolemia and hypertriglyceridemia have been associated with increased risk of carcinogenesis and metastasis in a wide range of cancer types (Long et al, 2018). Franklin et al (2018) additionally found that CML patients taking nilotinib—a routine BCR‐ABL tyrosine kinase inhibitor therapy for CML—were at greater risk for developing hyperlipidemia, which may impact risk for cardiovascular disease and dysregulation of lipid metabolism within other tissues associated with acute and chronic diseases (Andersen, 2018; Andersen et al, 2016; Andersen and Vance, 2019; Nelson, 2013). Tatidis et al (2002) found that LDL uptake is elevated in drug‐resistant K562 cell lines, leading to increased cellular cholesterol loading.…”

Section: Discussionmentioning

confidence: 99%

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Andersen

Dupree

Murray

et al. 2020

Lipids

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Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human-derived low-density lipoproteins (LDL), highdensity lipoproteins (HDL), and HDL-associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells-a bone marrow-derived, stem-like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein-mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose-and time-dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA-rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP-binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti-apoptotic B-cell lymphoma-extra large (BCL-xL), and the erythroid lineage marker 5 0-aminolevulinate synthase 2 (ALAS2), while SAA-rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

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Section: Discussionmentioning

confidence: 99%

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Andersen

Dupree

Murray

et al. 2020

Lipids

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“…Cardiovascular events are associated with CV risk factors, and prospective studies are needed to establish patient risk profiles [ 40 ]. Hyperlipidaemia and hyperglycaemia are major risk factors for CV disease and are associated with nilotinib therapy [ 41 ]. Homogenous management is essential to minimise the risk of related CV events.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors—A Single-Centre Retrospective Study

Varga

Ţilea

Petra

et al. 2020

JCM

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Introduction. Cardiovascular risk factors, pre-existing comorbidities, molecular factors, and the direct effects of second- and third-generation BCR-ABL1 tyrosine kinase inhibitors on the vascular endothelium contribute to the progression of cardiovascular (CV) events, especially atherothrombotic conditions. The study objective was to evaluate comorbidities, the cardiovascular risk profile, and events throughout the chronic myeloid leukaemia disease course. Methods. Retrospective data from adults who experienced haematology treatment at a single centre were continuously updated and followed throughout the disease course. A total of 43 subjects conforming with the inclusion and exclusion criteria of the study protocol were finally recruited. The median disease course was 77.0 ± 17.5 months. Statistical analyses were performed. Results. More than three CV risk factors were identified in 41.9% of cases. Almost half of the cases had relevant comorbidities (Charlson Comorbidity Index (CCI) ≥ 4), and no statistically significant comorbidities were found when comparing the tyrosine kinase inhibitor (TKI) treatment subgroups (p = 0.53). The patients at high and very high CV risk, according to Systematic Coronary Risk Evaluation (SCORE) risk classification, had 75.0% CV events (12/22 patients), p = 0.45. Throughout the disease course, 19 cardiovascular events were reported in 37.2% patients (13 males/3 females, p < 0.03). Conclusion. To the best of our knowledge, this is the first study exploring cardiovascular risk factors in Romanian chronic myeloid leukaemia patients. This study reinforces the need for close long-term follow-up that should be performed by a multidisciplinary team. The target should be not only the disease and specific drug-related toxicities but, also, the identification of cardiovascular and metabolic risk factors before the commencement of and throughout TKI therapy.

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“…Survival analysis has been previously used to evaluate the time‐to‐development of certain conditions, the time to the occurrence of pre‐defined events and the survival of certain patient groups . To the best of our knowledge, ours is the first study that has employed survival analysis to study the relationship of diabetes with hypertension and hyperlipidaemia in the private health sector of South Africa using claims data.…”

Section: Discussionmentioning

confidence: 99%

“…The pathways of oxidative stress, endothelial damage, lowgrade inflammation and hypercoagulability have been found to be common to these conditions and have also been credited with their coexistence. 41 Survival analysis has been previously used to evaluate the time-to-development of certain conditions, 44 the time to the occurrence of pre-defined events 45 and the survival of certain patient groups. 46 To the best of our knowledge, ours is the first study that has employed survival analysis to study the relationship of diabetes with hypertension and hyperlipidaemia in the private health sector of South Africa using claims data.…”

Section: Discussionmentioning

confidence: 99%

Time‐to‐onset of treatment for hypertension and hyperlipidaemia in South African diabetes mellitus patients: A survival analysis using medicine claims data

et al. 2019

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What is known and objective Hypertension and hyperlipidaemia have high prevalence among diabetics and increase patients’ risk of cardiovascular diseases, ultimately affecting prognosis negatively. Medicine claims data have gained prominence in the study of drug‐related events and outcomes. There is paucity of publications on the time‐to‐onset of treatment for these conditions among South African diabetics using secondary data. This study aims to determine the time‐to‐onset of treatment for hypertension and hyperlipidaemia among diabetics using a South African medicine claims data. Methods Survival analysis was conducted using retrospective data of patients enrolled continuously with a Pharmaceutical Benefit Management (PBM) company in South Africa from 1 January 2008 to 31 December 2016. We identified patients based on International Classification of Diseases, Tenth Revision (ICD‐10) diagnoses codes for type 2 diabetes mellitus (E11) who were receiving antidiabetic medication according to the National Pharmaceutical Product Index (NAPPI) codes provided by the Monthly Index of Medical Specialities (MIMS) classification code 19.1 (N = 2996). Among these patients, we then selected those who had ICD‐10 codes for hypertension (I10, I11, I12, I13, I15, O10 and O11) who were receiving antihypertensive medications, and those who had hyperlipidaemia (E78.5), who received antihyperlipidaemics during the study period. Data were extracted using SAS® system version 9.4 classification codes. The Kaplan‐Meier approach, used to compare the survival experience of patients who commenced treatment for hypertension and hyperlipidaemia, was conducted using IBM® SPSS® version 25. The time to the commencement of treatment of hypertension and hyperlipidaemia among the diabetics were measured in days. With 2008 serving as the index year, we followed up on patients until 31 December 2016. Results and discussion A total of 494 patients with an average age of 53.5 (SD 11.1) years were included in the study, 34.8% of whom were females. Prevalence of hyperlipidaemia and hypertension among patients were 35.0% and 45.6%, respectively. Average time‐to‐onset of treatment for hyperlipidaemia was 2684.4 (SD 42.2) days compared to 2434.2 (SD 47.6) days for hypertension. There was no statistically significant difference in age and sex among patients who started treatment for either of these conditions during the study (P = 0.404; Cohen's d = 0.132 for hyperlipidaemia and P = 0.644, Cohen's d = 0.059 for hypertension). What is new and conclusion Within an average of 6 years after an index period of 1 year free of disease, diabetics may commence treatment for hyperlipidaemia, hypertension or both. With all significant data appropriately captured, medicine claims data can be effectively used in survival analysis to determine time‐to‐onset of treatment for hyperlipidaemia and hypertension among diabetics.

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Incidence of type 2 diabetes mellitus and hyperlipidemia in patients prescribed dasatinib or nilotinib as first- or second-line therapy for chronic myelogenous leukemia in the US

Abstract: Patients receiving nilotinib had significantly higher rates of incident T2DM or HLD than patients on dasatinib.

Cited by 25 publications

References 13 publications

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Low‐Density Lipoproteins, High‐Density Lipoproteins (HDL), and HDL‐Associated Proteins Differentially Modulate Chronic Myelogenous Leukemia Cell Viability

Cardiovascular Events throughout the Disease Course in Chronic Myeloid Leukaemia Patients Treated with Tyrosine Kinase Inhibitors—A Single-Centre Retrospective Study

Time‐to‐onset of treatment for hypertension and hyperlipidaemia in South African diabetes mellitus patients: A survival analysis using medicine claims data

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