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Poor response to TKI therapy
3 weeks 6 days ago #1700
I would be grateful for your advice on this 32 year old man who was diagnosed with CML in April 2016. He has had a poor response in terms of reduction of BCR-ABL and his present level is 0.3% with no mutation of the ABL kinase binding domain. He initially started on imatinib but changed after four months to dasatinib because of poor response (BCR-ABL 138% at diagnosis, 35% at 3 months) and then a year later changed to nilotinib 400mg bd because of again, a poor response (1.3% at 12 months and 2% at 15 months). His BCR-ABL at the present time is 0.3 and has never dropped below 0.18. The last result which was two weeks ago was 0.3. Do I simply at this stage increase the nilotinib to 600mg twice daily? He is on treatment for hypertension having a significantly labile blood pressure. His full blood count remains normal. We have tissue-typed him and one brother who is not a match. We are awaiting tissue-typing on his second brother at this stage.
Planned follow up: For bone marrow examination at this stage
Repeat BCR-ABL monitoring at end of June
Poor response to TKI therapy
3 weeks 6 days ago #1701
His response to nilotinib 400 mg bd has been slow but steady – he has fallen from 2% in Aug 2017 to 0.3% May 2018. It is now over 2 years since he started TKI therapy so his risk of transforming to BC is quite small. The outcome for patients who are in CCyR at 2 years compared to the subset who are in MMR is fairly similar. So I would be reluctant to switch or dose increase at the moment. We know the 400 mg bd dose of nilotinib doubles the risk of vascular events compared to 300 mg bd so I would be worried about the vascular risk of 600 mg bd, plus there is limited data on improving efficacy with this dose. Ponatinib is worth considering, but given the vascular risk profile, probably only if his BCR-ABL increases to over 1%. I agree a marrow study would be reasonable to reassure you that he remains in CCyR. I wouldn’t consider an allograft unless he transforms or subsequently fails ponatinib therapy.