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Not responding quickly enough – switch TKI?

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Hi everyone,

I was diagnosed before Christmas last year, and have been on 400mg Imatinib daily.  My BCR-ABL is dropping but not at optimal rates, at 2 months I was 26.8% and at now at 4 months 12.5%. 

I'm 42 with no other health issues, and have not been feeling many side effects from the imatinib, but given the NICE guidelines and things I am reading more generally am worried I am not responding quickly enough.

Is it worth me asking to switch to a 2nd gen TKI at this point, or are the potential side effects just not worth it?

Thanks 

Phil

Hi Phil,

You are slower than what the guidelines suggest is desirable, but as long as your trend is down, you should be fine. There are many patients who respond slower than you do and ultimately achieve MMR. We call them turtles and they do very well indeed. I was a turtle - until I switched drugs!

What is your FISH level? This is an actual measurement of bcr-abl cells under the microscope and is much more a prognostic indicator. You want to be zero FISH at 12 months which is complete cytogenetic remission. At 12.5% PCR at 4 months, you are doing o.k. - and will likely meet this goal. Taking more imatinib (i.e. 600 mg daily) could very well accelerate your downward trend. Imatinib is a dose dependent drug upwards to 800 mg. It does increase side effect potential at higher dose.

In your case, I would switch to dasatinib. Dasatinib is a proven first line treatment alternative with a deeper response profile than imatinib. Also - having had imatinib first, data is suggesting that switching drugs can give a 'one - two' punch to CML by targeting other higher order cells in the CML hierarchy and may gvie you an even better response than either drug alone.

I would not start dasatinib at the current full dose of 100 mg. In your case, 50 or 70 mg should be started and your trend monitored monthly. You could very well respond dramatically downward on a lower starting dose. It depends on whether your doctor is aware of dosing strategy when it comes to CML drugs and dasatinib in particular.

You could always switch back to imatinib or nilotinib if dasatinib does not work out.

 

Hello
I was diagnosed 4 years ago,,reached MMR after 3 years of diagnose,,
My dr suggested many times to switch tki,,i was a slow responder,i waited because i had no significant side effects with my 400mg imatinib and my pcr was always dropping,and i didnt regret it..
Hopefully you will get it,as long as you dont have any issue..
Wishing you the best

Hi Phil,

There are many people who do not reach 'optimal' PCR ratios at 3; 6 or 12 months, yet they often go on to respond 'optimally' in the end, but it takes them a little more time. As your results show a downward trend virtually halving in 2 months.

I assume your 4 month result is from a sample given some weeks/months ago? My point being that the result is historical, so it may well be that you are currently below 10% or hopefully even lower.

Before you consider switching TKI - given you do not suffer much from imatinib side effects - you may want to wait for your next PCR result before taking a decision. If your levels are not at CCyR or 0.1% you might want to consider switching at that point so would talk that over with your clinician. 

I understand why you are nervous but you are obviously responding to imatinib.

Sandy

 

I take Imatinib and also didn’t reach the optimal standards in the first two years after diagnosis. Long story short, in the first two years I was feeling very well with little to no side effects, then I became aware of the guidelines...guess what, I panicked…Today, 6 years forward, I still take Imatinib and my BCR-ABL ratio is considered very good by the conventions.

You have great technical advice on this thread to help with further research. I would just say that guidelines can condition your mind to think a certain way and make your thoughts be based on a finite number of elements. 

I like Imatinib, it’s the first CML agent. People have been on imatinib over 20 years without issues. If it works for you without side effects, why change? Your almost there! Plus the price is more affordable. 200 bucks per month at Costco. From what I’ve read the side effects on the others can really suck, put you in the hospital, off dose, on dose, fluid in the lungs, etc. I don’t want none of that.

Thanks all for your responses. Very useful to hear about your experiences.