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Lost TFR: Should I go back on Gleevec or Try 2nd Generation TKI?

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I 56 year old woman who is a 17.5-year CML survivor and was diagnosed in March 2006. After 16 years, I stopped taking 400mg of Gleevec in March 2022 after I was PCR undetectable for about 7-8 years prior. I did not go off Gleevec sooner than March 2022 because I had children in high school and did not want to worry about my CML returning during that busy time of their lives. My PCR remained undetectable for almost 6 months and then reappeared at .06 and then bounced around at low levels until August 2023 when my PCR was .43.

When I was in the US, my MD Anderson doctor now wants me to try Tasigna 200mg once a day (cannot take much more than that due to other health issues) to try and reach a more durable TFR in 5 years. I now live in the UK and have contacted Dr. Jane Apperley who wants me to remain on 400mg of Gleevec as she thinks it get me back to undetectable quickly as I will be highly sensitive to the drug due to my success for years with Gleevec before. She's not sure I'll ever achieve TFR given how I lost PCR undetectable status after only 6 months in 2022. She is not a fan of Tasigna due to its side effects. She's willing to put me on whatever I want but favors a return to Gleevec.

I am so confused as to what to do. I started back on Gleevec just to get my numbers back in check but am experiencing the same awful side effects I did 17 years ago - namely weight gain, facial edema, and mood changes, and occasional GI issues. Frankly, it's been awful. I don't want to be on a TKI for the rest of my life.

My question is this: for those of you who had to restart taking a TKI after losing TFR, did you go back on the same medication as before? Or did your doctor recommend a different TKI or even ascimanib to reach a deeper state of remission for a bigger chance of TFR later? I know MD Anderson is now a big proponent of TFR given their concern over taking TKI's for long periods of time and its effect on the body. Dr. Apperley seems to think Gleevec is probably safest for long term use. I am so confused as to what to do.

Interested in opinions and what others have done in this instance.

Thank you in advance for any/all comments.

Hi

Sorry to hear about your lack of success in TFR. Can't advise on alternative TKIs, but I'm sure someone will.

I was on 400mg imatinib (Gleevec) for around 11 years, and pretty much undetectable after the first two years. I then followed the Destiny protocol and reduced to 200mg for a year, and remained pretty much undetectable, but lost most of the adverse side effects. I then stopped and was off imatinib for 17 months, but my BCR ABL started to rise again three years ago and I returned to 400mg. I regained MR4.5 in 4 months, and stayed on 400mg until 12 months after re-starting. For the last 2 years I have been back on 200mg, undetectable and with minimal side effects.

I'm now 66 years old. I have minimal side effects at the reduced dose. Right now I'm not tempted to try TFR again - I'll stay at 200mg. It may well be that I could reduce the dose further, and may think about this in future. I do think getting to MMR again and then reducing your imatinib to see if you get the same impact on side effects as I did may be a worthwhile option.

I would add that you are taking advice from one of the most highly regarded specialists in UK on CML in Jane Apperley.

I hope that helps

Hi-
Thank you so very much for your reply. I didn't know about the Destiny protocol so this is helpful. Will definitely mention it to my doctor.

Thanks again,
Beth

You are very welcome.

I think the Destiny results which start to provide information on whether TFR is likely to be possible for different patients may be of interest and use to you. This video (which is on this site) is a 2019 talk by Prof Richard Clarke, who was the lead researcher. https://cmlsupport.org.uk/videos/reducing-or-stopping-treatment-who-and-....

Hi
I come to this discussion a bit late but some views on your TFR dilemma
I have been on imatinib for 16 years and have had some blips along the way
At one stage about 8 years I was at 0.4 so lost MMR but we went on to 600 mg imatinib and that was successful in regaining MMR.
A more recent experience of coming off imatinib was about 4 years ago when I was treated for prostate cancer with iodine 125 implants -brachytherapy - and we did not know how iodine 125 would interact with a tki.After 6 months we lost our MMR badly so had to go on to 400mg imatinib again but it was slow to regain MMR but it happened after about a year. Currently my PCR is not quite below the magic figure of 0.1 so we are monitoring whether there is a trend towards losing MMR again.We might go on 600 mg imatinib or try another tki perhaps.
Jane Apperley has been quoted as saying nilotinib is hard on the heart and of course one has the fasting regime to consider as for some people it is inconvenient.
Dasatinib has a record of at 100mg of 1 in 5 getting pleural effusions so if one has a pulmonary condition it is a bit risky.
Long term use of imatinib has led to lots of musculo- skeletal issues and I have non diabetic peripheral neuropathy where the nerves in my kness and below have deteriorated-whether imatinib has done this I dont know.Night cramps lead to imperfect sleep for me and the neuropathy is a factor here as well.
GI issues are common with imatinib so some of us end up with diverticular disease-my urologist suggested that one tries Normacol with cereal in the morning;it is in the form of granules and acts as a bulking agent and helps to form better stools and avoids the usual semi diarrohea that is associated with imatinib.
Whether my atrial fibrilation which is quite mild at the moment is a result of long term use of imatinib again I am not quite sure.
I will never be able to do TFR again I am told and the long term use of imatinib does concern me but I think there is little alternative so we have to stick with it.At 78 I am doing well in life to dodge the bullets and the prostate issue has been totally zapped with a PSA near to zero.
The problem is if you go on to nilotinib or dasatinib and the side effects are intolerable or it is not effective then you are on to bosutinib and eventually one might run out of alternatives
All the best
John