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No BCR-ABL Mutations

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After my 2nd bone marrow biopsy, it was found that I was resistant to Bosulif, and my Hematologist orders a chromosomal test to find any mutations.

I discussed the results and they found no bcr-abl mutations, so they can't find a reason for me to be resistant. So she is going to put me on ponatinib, and have me visit the transplant office, so have start the match process in case the ponatinib doesn't work either. I discussed with her asciminib as well and she says that drug was only compared to bosulif and she believes ponatinib is more potent.

 

Has anyone else been resistant, but found had no bcr-abl mutations?

Hey there

Its strange that they won’t try Nilotinib or Dastinib before trying Ponatinb because if a mutation wasn’t found then maybe either of those would work too. It’s also quite rare to start on Bosutinib do you know why they made that choice?

Normally when they find a mutation they offer a number of different TKI but seeing as none was found it seems odd to suggest that Ponatinib would work? You could apply the same logic to the other 2 TKI.

Do you know if you had next generation sequencing because that flags up mutations that the older generation does not. And just because a mutation cannot be found it doesn’t necessarily mean one does not exist. I also learned that several mechanics in the body can make a person resistant to a certain TKI not just a domain mutation from the copious amounts of reading I did when I also had a mutation analysis.

I could also be wrong but Amiscinib is another 3rd gen TKI for pre heavily treated TKI so your haematologist saying it’s the same as Bosatinib seems very odd. Is your doc a general haematologist or a CML expert: it does seem some docs aren’t as clued up as even we are on here believe it or not..

I hope they decide quickly for you. Wouldn’t hurt to ask why they haven’t tried the other TKI and why you started on Bosutinib.

Alex

Hi

I would tend to agree with Alex that it seems strange that you have been put on Bosutinib at such an early stage.

Normally the progression might be to still start on imatinib and if found resistant to then consider nilotinib or dasatinib; bosutinib and ponatinib are really treatments down the line and are often regarded as third generation when all other tki s have failed.Ponatinib can have some nasty vascular and circulatory side effects and I believe the FDA in USA put a black box warning on it so basically you need to be monitored very carefully-one of my previous specialists said that he used to suggest patients take half a tablet of aspirin with it to mitigate against clotting etc.

I believe that the results from the trials for ABL001 or Asciminib are out and the results are very favourable;the purpose of the drug was to counteract failure with the last line tki ponatinib. Interestingly some of the trials used Asciminib as combination therapy with dasatinib .I am not sure if Asciminib has been fully approved for use by the FDA or EMA in Europe because if not it would still be termed an experimental drug and be difficult to source perhaps.

Some years ago when I for some reason lost my MMR (there were no new mutations) my specialist increased my dose from 400mg imatinib to 600 mg and after a year or so it worked. We agreed that if we go down the slippery slope to later generation tkis too fast and you get as far as ponatinib and it fails what do you do then? Medical specialists will always have differing views but I wonder if you need to take a second opinion from another specialist?

With best wishes

John