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Switch TKI thoughts?

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Diagnosed Chronic Phase November 2016. 46 years old and on placed on Imatinib 

PCR results on international scale

Diagnosis- 96

3 months - 15

4.5 months - 5.1

6 months - 2.1

9 months - .87%

12 months - .76 (increased from 400mg to 600mg dosage)

15 months - .54

No side effects and tolerating increased dosage of Imatinib well.

Would you switch TKI at this point or continue with slow and steady wins the race?

Also, anyone have experience with Bosatanib? My Hematologist is an expert in CML and has talked about this being the drug she would most likely switch to if we decide it is time to speed things up. Meet with Oncologist tomorrow.

First of all, you most assuredly are not slow.  People can take years to get to where you are.  You are on target.  Second, if you don't have any side effects on Gleevec then you are the luckiest person on this forum.  NO, you should not switch!  And, as for bosutinib, I have done an informal survey of the old LLS forum's emails regarding bosutinib, and I would say it's split 50/50 for those who think it's the easiest on side effects of all the available TKI's, and those who had to quit because of unrelenting diarrhea and nausea after months of trying.  So, to sum it up - you are responding excellently and you have no side effects.  Don't rock the boat!

Hi Mike,

Looking against the European Leukaemia Net Guidelines, to obtain an "optimal" response at 3 months your PRC should be lower than 10%, and at 6 months you would need to be below 1%. At 12 months this would need to be lower than 0.1%. So, your response is not optimal. That doesn't mean it's been bad, as the trend of results is downwards.

So if your response is not "optimal", what is it? Well the ELNet guidelines have three levels. Optimal, warning and failure. Your results fit into warning at 3 months (>10%), warning at 6 months (1-10%) and again warning at 12 & 15 months (0.1-1%).

However, you results for the most-part are at low the end of the "warning" range.

So there are two arguments here. Be proactive, get out of the warning zone and into the optimal one ASAP - so switch to another TKI. Or, be more patient and take solace in the fact your results are going down and consider you just may be a slightly slow responser. Your tolerance to imatinib might play into that ... if you tolerate it really well otherwise, and get no side effects, that may influence the decision.

Easy to say from a distance, but I wouldn't get too concerned. Your doctor is trying to get you from an OK response to a great one.Your results have been nowhere near the "failure" thresholds in those guidelines.

David.

Thanks for the thoughts. My doctor has said she tends to follow the NCCN guidelines for her patients on Imatinib. And if we follow the NCCN we are on target, but doubt I’ll hit the 18 month target at this rate.

She says the ELN guidelines are a bit unfair to an Imatinib patient as they were heavily weighted with 2nd generation drugs which are stronger. But that said, she has called me a slow responder and at every appointment we seem to face this choice of how patient is this patient and their doctor.

Unless we feel there is a risk to my long term prognosis then I am inclined to stay the course.

I would certainly defer to David's interpretation and perhaps I shouldn't have called your progress "excellent," but in the main, you are making a steady trend downward and you're within close territory of hitting the ELN targets.  What colors my answer is the memory of so many "turtle laments" on the old LLS forum, especially as the newer patients were experiencing speedier and more dramatic falls because they were on 2nd gen TKI's.  But what we turtles held onto was what the medical establishment told us, that slow and steady often gets you to the same place where the zoomers are, in the end.  I put a lot of weight on how well you are tolerating imatinib. That truly is golden - you have no idea!  I never had one happy day on Gleevec, for two years - suffered intensely from side effects.  So, you have many blessings to count!  Having said all this, you can certainly choose to switch drugs - it's (luckily!) your call.

There's nothing inherently wrong being a slow responder ... so long as you are responding and results improve. That really is the main thing. It's certainly not always the best idea to do things "by the book" and blindly follow guidelines. My own treatment would have been very different had we done that!

I went straight to 600mg Gleevec and did achieve MMR at 12 months. It may have taken longer at 400mg, don’t know, but it has been a little over 2 years now and I have no side effects either. No difference to me then taking aspirin. I was under 1.0 for 6 of the 12 months and then .028 out of nowhere. It will happen to you also. Great to hear someone else on this dose has no sides. I thought I was wierd. 

Hi Mike, my results were similar to your, perhaps a little slower, I also have no side effects off Imatinib, and did consider changing TKI, but did not. It took me over 18 months to get to MMR, back then ( 6 years ago ) the guidelines were slower, 12months 1% 18 months 0.1%. So for me I stayed on Imatinib, 2 reasons my levels were progressively falling, with a blip on the way, and no side affects.

My numbers fell to MR4 and after a few years, and try at stopping ( far to early  they rose, back on treatment and back down to a very steady MR4. ) So all are different, change stay, only you and your team can decide, this isn't a don't change post, its just a personally experience. As mentioned Glivec is a " weaker /slower " acting TKI generally compared to others, but still excellent at fighting CML.

Mike, My reduction on 400mg was similar after diagnosis (11 years ago!), and extended by a period on 200mg as my chronic low wbc worried my Consultant. Then boom at 18 months I went from about .7% to .03% in 3 months and PCRU the next test where I have been ever since. If I was in your position now I would wonder if you are among those who have a lower level of imatinib in your blood than many. Prof Bob Flanagan at Kings College has done some research which shows that the level of Imatinib in a population of patients all on the standard 400mg dose can vary by a factor of 10. If you are at the low end of that distribution it may explain why you have slower progress and no side effects. Kings offer a service to the NHS to do a test, which I would request now if I was you.  That might show that a  period at 800mg  imatinib might get you below 0.1%. Worth a try I think, before considering changing.

Thank you all for the input. After a very long discussion we have gone to a trial of 800 mg dosage. We will check for toxicity in a few weeks and a PCR check in 6 weeks and again in 3 months. She wants to get me “out of the shark tank“ sooner if possible than my current trajectory, but she thinks nothing bad will likely happen if we try this. She says I‘m one of the few to show no side effects and there is evidence that people process Imatinib at different rates.

Unusually, for Internet forums, this forum has an excellent search engine (whether I use the inbuilt search engine or raw Google). These historic postings can be very helpful.

I seem to be following the exact path of Mike (the original poster here). I wonder whether Mike still posts here.

I am also lucky in that I get no side effects from imatinib albeit that I've lost about 25% of my energy since a period commencing 12 months prior to diagnosis. My consultant prefers to concentrate upon the PH+ results until CCyR (she says, PH+ trumps BCR-ABL1" at this stage) is achieved. But for my lack of side effects with imatinib, I would be put on Dasatinib.

I do wonder whether my results will continue to mirror Mike's in the months ahead.