Hi
Was wondering if anyone has had any experience with Asciminib?
I was diagnosed in Accelerated phase March 2019
have been on:
none have worked and I got a mutation too. I am waiting on approval. They are unsure that I will get it due to studies stating that the mutation I have might not work with Asciminib
thanks for any info
Asciminib is designed to treat the T315I mutation:
https://ashpublications.org/blood/article/136/Supplement%201/47/470409/A...
It may work on other 'similar' mutations depending on what is the mutation.
What is your mutation?
The drug identified for F359 has been bosutinib. Perhaps you should suggest that to your doctor(s) or ask them why they don't try that drug first.
Asciminib, from my reading, is not for the mutation you have. Perhaps your doctor has a reason to prescribe it.
There is good news. F359 is not a 'strong' mutation and should respond well to bosutinib. Make sure you are taking adequate vitamin D3 - get your blood level raised to 70 ng/ml. This will help with accelerated stage by holding down blast cell counts. Once the right TKI drug is applied, your CML should plummet. Remember nutritional support helps your TKI do its job.
I agree absolutely with Scuba's advice. Bosutinib is available in the UK if you have failed 2 other TKIs... which you have. Where are you based?
Sandy
I'm trying to post a chart of mutations and TKI relationships.
It doesn't seem to be working. 
https://drive.google.com/file/d/18Eeuod4uGm-5mgR7ePAowZpDVt2MC54F/view?usp=sharing
It’s a really great chart. I was showed a similar chart when I got the mutation. Mine is not on this chart as it CI at the end. They said it was relatively rare one. With this one it is has the same resistance to both dasatinib and BOSUTINIB. I can’t remember the reason that they chose dastatinib over bosutinib but they said that if I failed dasatinib I will fail bosutinib so there wouldn’t be much chance in trying it.
it may seem as if it not a strong one, but it’s never gone bellow 87% in my cells it’s currently 96% and I’m failing each TKI. They only one that’s seems to work was Ponatinib but my body didn’t cope with the higher dose but the BCR kept going up on the lower dose.
If you respond to ponatinib and you are in the UK (?) it is my understanding that you would be prescribed the lowest dose- 15mg - to start with and increase incrementally depending on your response. I do know a patient (or two) who respond well to very very low doses of ponatinib.
Sandy
Sandy
Hi
yep Im the UK 😊 under Kings Hospital. I was started on 30mg because of the progressiveness of the disease. But I could not tolerate this dose. Was moved the 15mg. But didn’t not keep it under controlP i also take 1000units of Vitamin D have done for a while as I don’t seem to be able to absorbs it. Every now and again I have to go on 3200units for 12 weeks
Vitamin D is fat soluble and needs to be taken with food that has fat in it - otherwise most of it never gets absorbed. Fat triggers bile secretion which is needed to digest the supplement into the blood.
It is important you get your vitamin D level up to around 70 ng/ml. This will help fight against the accelerated stage by helping force leukemic blast cells to differentiate. As a reference, I take 5,000 IU's of vitamin D3 per day in contrast to your 1,000 units. And I take much more in winter.
Hi Nicola
I posted here on forum previously about Asciminib and how it had been presented at the ASH conference in US in Nov/Dec 2020 and Scuba posted one of the academic papers from Jorge Cortes and others.Basically everyone thought that it was a new and novel tki that would take the place of those who had failed bosutinib /ponatinib.
I think that the path for approval would be to FDA for consideration and then the UK via NICE would consider it;because of Brexit I think that the European Medicines Agency would now be redundant-except for Northern Ireland.
So I suggest pending approval by NICE which could take some time as it is manufactured by Novartis who have a base in UK why dont you suggest to your clinicians to approach the manufacturer to see if it is available under their patient access scheme.The problem is that until it is approved by FDA/NICE it is still classed as an experimental drug.Patient access schemes are normally targeted to developing countries that cannot afford expensive tkis .You might also check if there any upcoming trials with Asciminib in UK.
Regards
John
Hi thanks for the info John.
The ball is being rolled for the approval on compassionate grounds for Asciminib. As I have failed 3 TKIs including Ponatinib.
But for me I’m more worried about the proven resistance the mutation I have, has with Asciminib. I’m struggling to get data on if there is anything new that now states that it works.
i have emailed my current consultant but not getting any info. My previous consultant has expressed concern and he has found no data to say it will work
Thanks for the reply
If you Google "Jorge Cortes Asciminib" you will see a number of papers and references listed and also a video;apparently the drug has a different binding mechanism from the other tki s and hence is more resistant to not being affected by new mutations .Have a look.
Regards
John
Nicola,
Asciminib is quite different to the other TKIs for CML. It targets a completely different part of the kinase domain.
In the picture below, you can see where nilotinib binds, and this is roughly the same point for all the other TKIs as well (besides asciminib) which as you can see binds to a totally different location. So the theory goes that if the “pocket” where the other TKIs bind has a mutation of some sort which prevents it from working that mutation isn’t going to block asciminib as it targets a different space.
https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.8b01040?rand=scd57mbv&
David.
