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Cardiovascular Risks More Common With Newer TKI Chemotherapeutics for CML

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#1 Buzzm1


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Posted 16 June 2016 - 10:28 AM

Cardiovascular Risks More Common With Newer TKI Chemotherapeutics for CML


MedicalResearch.com: What is the background for this study? 


Dr. Dahlén: Patients diagnosed with CML have had a dramatic increase in life-expectancy since the widespread introduction of tyrosine kinase inhibitors (TKI) in 2001. However, treatment is today regarded as life-long. We thus need to observe for late-effects of continuous TKI exposure. Recent reports have demonstrated a linkage between TKI treatment, especially more potent 2nd and 3rd generation drugs, and to the occurrence of peripheral arterial occlusive disease (PAOD). This study aimed to use real-world data utilizing Swedish population based registries together with the dedicated Swedish CML registry which contains data and follow-up on more than 98% of all CML patients diagnosed in Sweden since 2002.


MedicalResearch.com: What are the main findings?


Dr. Dahlén: We compared an cohort of age- and sex-matched people to a cohort of CML-patients in regards to the occurrence of myocardial infarction, cerebrovascular disease, other arterial thrombosis, deep venous thrombosis and pulmonary embolism. We showed that deep venous thrombosis, other arterial thrombosis and myocardial infarction was more common in CML patients compared to the controls. When comparing the different TKIs on the market between 2002 and 2012 we also saw a tendency to increased risks of the above events with usage of 2nd generation TKIs (nilotinib and dasatinib) as compared to the 1st generation drug imatinib.


MedicalResearch.com: What should readers take away from your report?

Dr. Dahlén:  Patients with CML should be closely monitored in regards to long-term effects of TKI treatment and patients with risk-factors for cardiovascular disease should be handled with caution, focusing on both preventive measures but also in regards to the choice of TKI.


MedicalResearch.com: What recommendations do you have for future research as a result of this study?


Dr. Dahlén:  We need to further investigate the effects of the 2nd generation TKIs, both in the population-based setting to estimate risks with treatment, but also to find the underlying mechanisms of how TKIs may promote cardiovascular disease.


MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.



Dahlén T, Edgren G, Lambe M, Höglund M, Björkholm M, Sandin F, et al. Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study. Ann Intern Med. [Epub ahead of print 14 June 2016] doi:10.7326/M15-2306

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.



For the benefit of yourself and others please add your CML history into your Signature


02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive


2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17


At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  


In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  


longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.


Cumulative Gleevec dosage estimated at 830 grams


Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  


Trey's CML BlogStopping - The OddsStop Studies - Discussion Forum Cessation Study

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