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Advice regarding dose reduction of nilotinib in chronic phase CML

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Manjunath Narayana and Ricky Nelles
Topic Author

3 years 1 month ago #1816 by Manjunath Narayana and Ricky Nelles

Advice regarding dose reduction of nilotinib in chronic phase CML was created by Manjunath Narayana and Ricky Nelles

We would like some advice regarding nilotinib management of a patient with chronic phase CML. This 46yo woman was diagnosed with CML in 2010 and was initially treated on the TIDEL II trial requiring an early change from imatinib to nilotinib due to tolerability issues.

She has remained in MR3 since 08/2017 despite dose reduction to 300mg BD due to side effects including rash and alopecia. She achieved a MR4 for 12 months in 2019 but has subsequently remained at >MR3 until now on our newer Ultra2 assay (currently MR3.85).

We are after your advice regarding whether further dose reduction or treatment cessation is possible given the duration of her response to nilotinib in the setting of her ongoing moderate side effects.

Any assistance would be appreciated.

Tim Hughes
Topic Author

3 years 1 month ago - 3 years 1 month ago #1817 by Tim Hughes

Replied by Tim Hughes on topic Advice regarding dose reduction of nilotinib in chronic phase CML

Her response to nilotinib has been optimal but she has not achieved a sustained MR4.5 which is our usual requirement before attempting TFR. The chances of achieving TFR if you stopped now is probably less than 30%. At this stage you need to decide whether TFR is worth pursuing or not. It is still quite possible that she will become eligible for TFR in the next few years if she persists on this current dose of nilotinib. If she is reluctant to do this because of her side effects then a further dose reduction or switch to dasatinib 50 mg daily would be reasonable, it just makes TFR eligibility less likely in the next few years.

My main concern about long term nilotinib is the vascular toxicity. This may not be a major concern in a 46 year old female depending on her other risk factors. However, I would factor this into my decision about the ongoing dose of nilotinib.

Last edit: 3 years 1 month ago by arlene.

jeff lipton
Topic Author

3 years 1 month ago - 3 years 1 month ago #1818 by jeff lipton

Replied by jeff lipton on topic Advice regarding dose reduction of nilotinib in chronic phase CML

I do not disagree with Tim's advice and understand the reasons for his perspective. My question now becomes, is this to be the standard advice for patients on nilotinib where discontinuation is not possible for whatever reason?

In many cases, not this one, where nilotinib was first line therapy, a move to imatinib as "Maintenance" could also be considered under these circumstances.

Last edit: 3 years 1 month ago by arlene.

Tim Hughes
Topic Author

3 years 1 month ago - 3 years 1 month ago #1820 by Tim Hughes

Replied by Tim Hughes on topic Advice regarding dose reduction of nilotinib in chronic phase CML

I think this is the sort of issue which we could debate because it is not solidly evidence-based so I would welcome a diversity of opinions on this issue. In my own practice, I am looking closely at any patient who has been on nilotinib for more than 5 years and reviewing the risk-benefit balance of continuing versus either reducing dose or switching to imatinib (assuming that is a reasonable option for that patient). This is probably less controversial if the patient is in a DMR but has no interest in TFR where the benefits of continuing nilotinib long term are quite limited and the risks, at least in some cases, are considerable. The situation is probably similar for patients on long term dasatinib, although in this case we don’t have the 10 year vascular event data that we have for nilotinib, so the risk side of the equation is less certain.

Last edit: 3 years 1 month ago by arlene.

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