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Mutations and treatment free

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Hi 

I’m probably a long way off from treatment free. But I was just wondering if anyone knows if it is possible or not. 
 

I’m currently on 15mg Ponatinib due to a TKD mutation. It’s not working as well as. I can’t go on ABL001/Asciminib as the mutation has revelry been shown to be resistant to it. 
 

so treatment is up in the air at the moment

But was wondering if anyone with a mutation is able to go treatment free? Or even if you are able to go treatment free?

 

I will obviously speak to my consultant. But it was just something I was thinking about? 
 

thanks to anyone that can reply 

Hi Nicola

Sorry to hear your story, mutations can occur on any TKI and the fact you’re on Ponatinib suggests you’d have the T3151 mutation which is a resistant mutation to all TKI except what you’re on and Amascinib. To be honest I’ve no idea where you go from there regarding TKI treatment.

Can I ask what your last PCR is and what other treatments you have been on and for how long?

In answer to your question without being blunt is if you don’t respond either of those treatments the TKI isn’t going to give you treatment free.

Can you explain what advice your doctor has given you?

Alex

Hi Alex. Thanks for your reply.

I was DX April 19’ in accelerated phase. After 6 weeks in hospital I was put on Nilotinib 300mg twice a day. BCR went down supper quick. I hit 0.0003 within 3 months.  But stated to up monthly after that (I have BCR every 6 week)

Feb of this year my counts went up to 1.13. Mutation test was done and I don’t have the T3151 mutation, the mutations have is F359C which is also resistant to most including (new data just released)  Amascinib so that is no longer an option. 
Ponatinib has Brought my numbers down. Currently 0.02. But the side effect (high blood pressure and daily crippling head aches) are having an effect). 
My consultant hasn’t really mentioned treatment free. Just want to know if there is a light at the End if the tunnel really. The two next options are 

Ponatinib once or twice a week with  

Or  switching to Dasatinib (no resistance)but in Consultants words ‘this would be a de-escalation to a 2G TKI and give the aggressive pattern of my CML there is a high risk of developing further mutations and resistance to Dasatinib’ 

 

I just can’t seem to find anyone with mutations that have been able to go treatment free

 

Hi Nicola,

Wow gosh what a journey you’ve had. I too am on Nilotinib 300mg twice daily and have been for 2 years currently at around 0.1% but not yet broken the MMR barrier. I have had mutation analysis done but the report takes a long time to come through according to my doc. So will see what that yields hopefully treatable too if I have one. Obviously hope that I don’t.

Its great that your CML is being managed again albeit with symptoms that must be crippling for you so sorry to hear that! I hope you find a happy balance of treatment and symptoms.

As far as I understand anyone can go TFR once cml is controlled at low levels for at least 2 years and that may well be you in the future. I am guessing by your mutation profile it’s trickier to treat than what is standard therapy and it’s good your doc is cautious about switching as you’ve mentioned this can create more mutations going forward.

I hope you get some more clarity about TFR but that’s my understanding. And please let us know how you get on with things and always reach out on here or to me personally should you feel the need.

Alex

Hello

I came across an opinion on this matter here:

"Patients who develop imatinib resistance with kinase domain mutations are rarely candidates for TFR."

You will need to read in full.

https://www.cml-foundation.org/icmlf-forum/1499-stopping-tki-in-a-patien...

 

Hi,

You seem to have responsive disease shown by a a good response to TKI therapy - i.e nilotinib and now ponatinib, so I am puzzled by your consultant saying you have aggressive disease. Am I right in thinking that you are more concerned with the side effects you are experiencing? High blood pressure and cluster headaches?

Dasatinib may well be a good TKI for you - or even bosutinib? - as it has been shown to be effective in controlling AC phase CML as well as Blast phase CML - in some patients. I do not understand why moving to a 2nd gen TKI (dasatinib) from ponatinib would be deemed as de-escalation?... although some do clarify PON as a 3rd Gen TKI.... 

If you are responding well to ponatinib at 15mg (daily?) then your issue would be side effects rather than resistance which is why you ask about TFR in your case?

Where are you being treated?

Sandy

Hi Sandra. Thanks for replying

I was diagnosed in accelerated phase / boarder line blast phase. I seem to respond well when starting treatment of Nilotinib but after 4 months my counts increased rapidly. And after mutation testing was told that I have mutation (In 96% of cells) that only Ponatinib and maybe dasatnib work with. Even the new asciminib has been recently been proven not to work with the mutation I have. 
 

so at the moment Ponatinib is working but for me the side effect are to extreme to live with.
my only option would be to try Dasatinib. But even when my BCR is low. I still have a higher number of blast cells. So he is reluctant to switch me to dasatinib

 

if I knew that in 2-3 years I could come off treatment (depending on BCR results) it would give me greater hope

 

I’m under Kings