My Situation after Flunking TFR

Rick, assuming you test undetected in July, continue reducing your Imatinib dosage with each undetected test, first to 100mg and then to 50mg (100mg every other day), then to 33mg, eventually weaning yourself off of Imatinib if you are successful all along the way.  At the very least you will find out how much Imatinib you actually need to take.

Other than that if you switch to another TKI they will likely want you to start on full dosage.

Various “stopping” studies suggest that in addition to depth of response, there is a correlation between length of time on treatment (and in MMR) and ability to stay in TFR.  It needs more time.  I don’t know where your haematologist got 70% from but that looks like data from the UK DESTINY study, which showed that patients on the study in MR 4 or better had about a 70% chance of staying in TFR. While that study didn’t show a correlation between length of time on therapy and likelihood of relapse, no one on that study was on treatment for such a short time as you were (entry criteria included on treatment for 3 years or more) so the conclusion they drew about your situation strikes me as not supported by the studies (on the contrary, in fact).

FWIW, I’m in TFR and was on the DESTINY trial.  I’d been undetectable for 4 1/2 years (on 400mg imatinib) when I went on the study, which involved a year at half dose before stopping completely. By the time I did that, I’d had 6 years on imatinib.  I’ve now been off it completely for 7 years, remaining undetectable. 
 

And as for going back on therapy if you fail, I’m pretty sure everyone on DESTINY who had to go back on treatment went back on the drug which they had been on, and which had obviously been working for them! 
 

Hi Rick

I followed the Destiny Protocol after around 11 years om 400mg imatinib. As with Richard I did a year on 200mg and remained at 0.000%. I then stopped but 17 months later after a slow rise over a couple of months I went over 0.1% BCRABL so back on to 400mg of imatinib.  I regained my zeros in 4 months.

For me the reduction in side effects was more marked in the change from 400mg to 200mg. with my consultant's agreement after 12 months on 400mg I reduced to 200mg again, and have remained at 0.000% for the last 8 months. I don't feel any need to try for TFR again. 

Also echoing Richard I have heard the lead researcher on the Destiny (Prof Clarke) say that all those who lost remission on reduce dose in the trial regained it when they went back to full dose.  

This paper is a good summary of the various TFR studies and their outcomes

https://www.haematologica.org/article/view/haematol.2019.242891

Depth and duration of response seem to be factors (newer TKIs only seem to produce higher success numbers because they induce a greater number of deeper responses, not a better TFR success percentage - but choosing TKI for the purpose of getting TFR is not popular among physicians at least in the UK because there are many other factors involved, in particular side effects - so definitely discuss any such thoughts with a specialist). 

As for other influences such as supplements, I am a very firm believer in evidence based medicine.  I am not aware of any studies which investigate the influence of these things on TFR, and it would be a very difficult study to set up and run.  In my own case, I don’t take supplements other than vitamin D in the winter.  My diet is pretty good and I’m very fit, especially for my age (55). I run at least 3 times a week (around 25 miles in total), and cycle anywhere from 50-80 miles per week.  However I didn’t do much of that until I had more or less finished the DESTINY study.  And I like a beer and glass of wine or two.  My own view, which is an opinion only, is that biologically there’s something about me which means TFR works, and my CML translocation was also rare which may have made a difference.  I became undetectable on imatinib very quickly - within 6 months.  If I were you, I would continue on your current TKI as it’s working but give it more time in deep response.  At least 2 years.  Then perhaps try half dose, and then stop.  I lost all my side effects when I went from 400mg to 200mg, and could happily have stayed on that dosage.  If you can’t get to undetectable on imatinib then consider a switch but listen carefully to the advice on the side effects of the newer TKIs.

7 years in TFR and continuing (am waiting for my latest bcr/abl). BCR/abl every 4 months.  There are quite a few others like me but all had deep responses for a long time and were on treatment for several years.  In my case, I was undetectable within 6 months of starting treatment in 2009 and have been like that ever since.  I am not sure if there is any ongoing research into more precisely to identify which patients might be able to stay in TFR - it was planned as part of DESTINY which is why bone marrow samples were taken at the outset but I don’t think anything has come from that yet.