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Potential Nilotinib complication - eosinophilic myocarditis

  • Richard Doocey
  • Richard Doocey's Avatar Topic Author
1 month 2 weeks ago #1787 by Richard Doocey
61 year old male

Chronic myeloid leukaemia

• Initial diagnosis February 2010 with presenting FBC showing Hb 146, WCC 84.5, ANC 50.7, platelets 417, blood film left shifted with typical appearance of chronic myeloid leukaemia
• BM biopsy 19/02/2010 consistent with CML in chronic phase
• Karyotype 46XY, t(9;22)(q34;q11)[20]
• Commenced on Imatinib tyrosine kinase inhibitor therapy
• Changed to Nilotinib late 2010 due to Imatinib intolerance
• Achieved complete molecular remission (CMR) December 2012
• Discontinued Nilotinib 2016 after approximately 4 years of CMR
• Rising PCR September 2016 so recommenced on Nilotinib 400 mg daily
• Regained CMR January 2017
• For ongoing Nilotinib 200 mg BD (patient choice and prior haematologist decision) and 3 monthly blood test disease monitoring

This man has presented with SOB / Cough and a CT scan showed pericardial / pleural fluid.
Cardiac biomarkers of BNP and Troponin were elevated.
ECHO = normal LVEF.
Cardiac catheterisation = moderate proximal LAD stenosis 50-60%.
RV myocardial biopsy = eosinophilic myocarditis NOS ?cause.
Cardiac MRI results awaited.
FBC shows slight neutrophilia. No PB eosinophilia.
The Nilotinib was withheld at presentation.
He is now improving and ready for discharge.
The cardiologists have implicated his Nilotinib as the cause for his eosinophilic myocarditis, presumably by exclusion.
The patient is unsure if he should continue on Nilotinib given what the cardiologists have told him.
I have read some of the TKI / Cardiac SE literature and can’t find any specific reference to Nilotinib and myocarditis.
Do you have any thoughts please on whether Nilotinib could be the culprit here?
Have you seen any myocarditis on Nilotinib?
He has been on the drug for many years with no problems or cardiac SE concerns.
He is presumed to still be in a CMR – updated Q-RT-PCR result awaited.
The LAD lesion will be managed with statin and medical therapy.
Would you consider a change of TKI?
  • Tim Hughes
  • Tim Hughes's Avatar Topic Author
1 month 2 weeks ago - 1 month 2 weeks ago #1788 by Tim Hughes
I haven’t heard or read about eosinophilic myocarditis or any myocarditis associated with nilotinib, but it would be hard to exclude the relationship with any confidence. So, I would probably switch him to another TKI. The IHD would be another good reason to switch him – even at low dose I think nilotinib should be avoided in patients with established coronary disease. Imatinib probably isn’t a great choice if he wasn’t able to tolerate it initially. Dasatinib might also increase the risk of vascular episodes in this man so if I were to prescribe it I would probably use the modified dose of 50 mg daily. Given his excellent molecular response at present, he will likely maintain it on this dose of dasatinib. Bosutinib might be a better choice – not sure if it is available in NZ.

The other consideration is a second attempt at TFR. He has been back in a DMR (MR4.5?) for over 3 years now so there is a prospect (~35%) he would achieve TFR on a second attempt. It looks like the duration of MMR after the first attempt is fairly predictive of the success rate with a second attempt – I can’t tell how long it was from your notes. If it was shorter than 6 months, you may want to wait another year or two before considering a second TFR attempt.
Last edit: 1 month 2 weeks ago by arlene.
  • jeff lipton
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1 month 2 weeks ago - 1 month 2 weeks ago #1789 by jeff lipton
I think we tend to forget that our patients who do so well on TKI therapy, get other diseases. This is not an uncommon presentation of HES. Agree with Tim for safety sake, but think this individual if not already done, needs a new look for hypereosinophilia.
Last edit: 1 month 2 weeks ago by arlene.
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