Diagnosed 2017... I'm just wondering if someone is / was in the same situation:
3 TKIs failed (Imat.no positive effects, Dasat./Nilot.only negative blood count drops, all the time BCR ABL somewhere between 95% & 35% Ph+ FISH) No BCR ABL kinase mutations
So i have 2 TKIs left (Bosu&Ponat) to try 2018/2019 before SCT
Anyone around in a similar situation?
Sorry to hear this. What does your oncologist suspect? Did you have a bone marrow biopsy at diagnosis? I have never heard of someone having no response at all to these 3 TKI's.
Thanks to you both and sorry for my late reply, the forum updates reminder didnt seem to work.
Yes sure I had marrow tests every three/4 months.
Out of interest, Which blood(not marrow)tests apart from regular full count and bcr/abl are available but not usually done to give accurate signs of what is going on?
What breakpoint(s)/rearrangement(s)/ were discovered in any of your bone marrow biopsies? The typical breakpoints are either e13a2 P210 or e14a2 P210, but some CML patients have atypical BCR-ABL rearrangements such e1a2 P190 BCR-ABL. The latter show a poor response and short-lived responses to TKI therapy. If you have the more typical rearrangements and have tested negative for mutations, it is indeed surprising that none of the 3 primary TKI's has worked better.
Which TKI showed the the best PCR response and at what dose? As strange as it may sound, you might want to consider a lower dose of this TKI before moving on to bosutinib and ponatinib. Ultimately, if you are a good candidate, SCT might be the best route. Here's hoping that one of the TKI's will work for you - good luck
I failed/rejected dasat but was started on bosutinib gradually...100mg 2 weeks, 200mg 2 weeks, 300mg and staying on 300 since response was good according to reports. I did not have the horrible diarrhea that most suffer when starting at 400mg (400 is the normal start dosage). There is a trial at MD Anderson where they start you at 300. I was glad to be eased into the drug.
Stephanie
Hi,
I’m in a similar situation having failed my third line therapy due to intolerance, although my remaining 2 TKIs are Nilotinib and Ponatinib.
Since you have no mutations, I would try Bosutinib next since Ponatinib has a worse safety profile. From my experience on Bosutinib, I would suggest you speak to your Consultant to try a lower starting dose than the 500mg indicated for patients previously treated with another TKI, since this will lower the risk of diarrhoea and abnormal Liver Function Tests (LFT). Make sure you have a monthly LFT for the first 3 months. I had to come off Bosutinib due to elevated ALT readings and this is the first TKI I have failed due to intolerance.
What is your current PCR blood test result on the International Scale and are you still in Chronic Phase?
On a personal level, how did you get on with Nilotinib from a side effect perspectve and fasting twice a day? This is likely to be my next option.
I hope you have success with Bosutinib if this is the TKI you choose for fourth line therapy. Apart from the ALT issue, I didn’t have any other major side effects and the diarrhoea wasn’t as bad as I feared (it was worse on Dasatinib). I also achieved MMR, which makes it particularly difficult accepting the decision to have to come off Bosutinib.
James.
