It looks like you are finally getting good control of your patient’s disease with nilotinib after 12 years but her BCR::ABL1 values are still not in the MR4.5 range. While a TFR attempt would be tempting I don’t think she would have a great chance of success at this stage given her imatinib treatment failure, a KD mutation and lack of prolonged MR4. On the other hand continuing her nilotinib therapy – even at the lower dose is starting to get quite risky from a cardiovascular perspective. Exposure of more than 5 years of nilotinib is associated with high rates of arterial occlusive events, even for patients who were low risk for CVS disease initially.

The options here would be to lower her nilotinib dose further to 300 mg daily, switch to low dose dasatinib (50 mg/day) or switch to asciminib 80 mg daily. You could argue that it would be better to wait until she is in the MR4.5 range before making any change but I am more concerned about vascular events after such a long exposure to full dose nilotinib, so I would probably make a change now. Personally, I would switch her to asciminib but I am not sure if that is possible in NZ in this setting. If not I would probably switch to low dose dasatinib. If the preference of the patient is to remain on nilotinib then I would go for a lower dose.

My patient is 52 with CML and presented in 2010 with a white cell count of 370, Hasford score – intermediate risk, Sokal score 1.12 – intermediate risk.

She was commenced on hydroxyurea and entered into the TIDELL II study.

May 2011 she switched to nilotinib because of residual BCR-ABL positivity of 1.5%

Still not achieved MMR in August 2013, mutation analysis confirmed L445P mutation

MMR achieved November 2013 >3 years post-treatment start date

BCR-ABL ranging between 0.017-0.009 since Feb 2022

Nilotinib dose reduced to 300mg BD in November 2020 because of associated increased cardiovascular risk – she does not have any other risk factors at this stage.

Would you consider her for a trial of stopping treatment at all?

Thank you