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Cardiovascular event on nilotinib-should I switch?

  • International CML Foundation
  • International CML Foundation's Avatar Topic Author
8 years 10 months ago #1037 by International CML Foundation
Cardiovascular event on nilotinib-should I switch? was created by International CML Foundation
A 64 year old male with chronic phase CML diagnosed in July 2014. WCC was 30. No splenomegaly.
Background of dyslipidaemia (high triglycerides), and depression. He is also overweight but not obese.
Started Nilotinib in August 2014 and did not get onto full 300mg bd dose till November 2014. He initially suffered muscle cramps, mild biochemical pancreatic enzyme rise and nausea and occasional vomiting. Most of these problems have now gone.
In January 2015, he developed an atypical continuous shoulder ache that had been present for many days. I sent him to emergency as he 'did not look right ' was nauseated and short of breath. He was found to have an elevated troponin with a hsTrop I of 462 (where ref range is <50). There was no ST elevation. A CTPA was negative for PE. Coronary angio report showed left circumflex 40-50%, RCA 30%, LMA normal and LAD minor disease. He now has cardiologist who has added beta-blocker and ACE-.
In regards to efficacy of Nilotinib, the bcr-abl was 0.25 % in Dec 2014 and 0.19% April 2015

Do you think I should switch TKI?
  • Tim Hughes
  • Tim Hughes's Avatar Topic Author
8 years 10 months ago #1038 by Tim Hughes
The patient has had a satisfactory response to nilotinib but has had a
serious ischaemic event that puts him at high risk of further events. Your
options are:

1. Keep going with nilotinib and aggressively modify his risk factors. I
don’t favour this option because I suspect not all of his risk factors are
easily modified and we have no evidence that this would reduce the risk of
a further event in the setting of nilotinib therapy, and the risk of a second event is probably quite high.

2. Switch to imatinib. This is probably the safest TKI for patients with a
high risk of ischaemic vascular events. You have already established good
molecular control of his disease and he was presumably low Sokal risk to
start with (?), so this would be reasonable. Downside - likely to get a
lot of low grade toxicity early.

3. Switch to dasatinib. This also comes with some risk of vascular events,
but lower than nilotinib. Likely to be better tolerated than imatinib and
you would be more confident that he would maintain a good molecular
response than you would with imatinib. Downside - risk of pleural
effusions is high (>60 years old around 40%) but usually treatable.

I would favour options 2 or 3 and would have a slight preference for
imatinib.
  • Jeff Lipton
  • Jeff Lipton's Avatar Topic Author
8 years 9 months ago #1039 by Jeff Lipton
Replied by Jeff Lipton on topic Cardiovascular event on nilotinib-should I switch?
I think Dr. Hughes makes a great point. Although the response has been quite good, the risks associated with nilotinib are high and a switch is indicated, and the choices suggested and the reasons have been given. You can add bosutinib to the list of acceptable choices.
This raises a more fundamental issue that we need to consider whenever we choose a TKI and also what we do in our monitoring process. Monitoring to me, now goes beyond just following molecular or cytogenetic response. I come from the school that says if the option exits, better to choose a drug which does not complicate existing problems, rather than choose one that may and try to modify the risks associated with its use. Also, once we have started a particular therapy, monitoring either by us or in conjunction with someone else, must now include folowing of potential risks particular in the cardiovascular arena as well as the appropriate aggressive therapy of these risks, again either by ourselves or in conjunction with others.
Of course, this may be all limited by what is available to the patient as limited by drug approval, reimbursement, previous therapy and response, resistance, etc.
  • Francisco Cervantes
  • Francisco Cervantes's Avatar Topic Author
8 years 9 months ago #1040 by Francisco Cervantes
Replied by Francisco Cervantes on topic Cardiovascular event on nilotinib-should I switch?
I would stop nilotinib because of the high risk of vascular events in this particular patient. If the CML is low risk (and the patient is now close to major molecular response, at less than 12 months from treatment start) I would switch to imatinib, the safest drug with regard to vascular problems. Dasatinib would be an option if the CML would be high risk, which seems not to be the case.
  • Jerald Radich
  • Jerald Radich's Avatar Topic Author
8 years 9 months ago #1041 by Jerald Radich
Replied by Jerald Radich on topic Cardiovascular event on nilotinib-should I switch?
Agree with the others. This patient has unfortunately declared his vascular risk, and all efforts should be made to keep the risk of future vascular events to a minimum. Imatinib would seem a good choice.
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