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Ponatinib vs Transplant

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Hi all,

Curious to get your thoughts. I recently developed the T315I mutation and the next step is to go on ponatinib - plan is to start 45mg and then reduced over time to 15 if all goes well. I’m in my early 40’s and don’t like my chances being on Ponatinib long term with all its associated toxicities. Have also considered asciminib but doctor feels I have a better shot with Ponatinib. My BCR/Abl is still relatively low but has been creeping up (0.03) up a log over the last few months. My question for the group is do you think my long term prospects are better (assuming it works) with long term use of Ponatinib, or alternatively going the transplant route. Both options frankly scare the crap out of me! Hoping my side effects will be minimal. Thank you!

You will find several patients who do really well on 15mg of ponatinib. 45 is a lot, and I think the manufacturer know they got it wrong during clinical trials with that dose - but they can’t really easily change that now.

I have seen a number of t315i CML patients go on ponatinib as a sort of pre-transplant routine, but settled with it really well and never went on to have the transplant.

I suppose take it one step at a time - if your BCR-Abl stays low, why transplant?

Thanks for the reply David!

Speaking with my oncologist the plan is to get me down to 15mg as quickly as possible after seeing a response.

To answer your question, the potential reason to go for a transplant even if numbers are low are because of the potential toxicities with Ponatinib. I may have the potential for a longer and healthier life with a transplant as compared to the CV tox I may pick up with Ponatinib.

Hi

I would definitely suggest to try ponatinib first. Given that your BCR-ABL level is very low you have a high likelihood of ponatinib working and overcoming the low level of T315I mutated clone. You could then go to a lower dose. I would suggest you try to read the OPTIC study headed by Jorge Cortes among others who proved that the strategy of starting from 45 mg and quickly going to 15 mg has a very reasonable risk to benefit ratio and 15 mg is a tolerable dose. The response criteria there was 1 % so you are already way below that.

Transplant is a rough road with long-term implications as well. Although you are young and success rate is high I personally believe transplant should be the last resort.

ps! I am surprised that a T315I mutated clone popped up after 4 years of treatment. Have you had mutational analysis before as well with no detection whatsoever?

Regards

Timo

Thanks Timo! Will go back and read the study. Hopefully I’ll tolerate the med well and be able to get down to the 15mg dose quickly.

I was tested a couple of years ago for a mutation, after failing imatinib and nilotinib and was negative. The doc tested me because my numbers were slowly creeping up on dasatinib - went up one log over a year (.003 to 0.03), each test it was up a bit. Was very surprised to see that this time a mutation was detected.

Hi

Let us know how things are going with ponatinib when the time is right.

Take care

Thanks for checking in. Started on Friday and so far so good. A little skin sensitivity and mild headache, but that’s it so far (hopefully it stays that way). Let’s see how the blood work comes back in a couple of weeks.