Imatinib Dose Reduction Starts

Good luck!  I reduced more gradually - 300 mg for a year or more before going down to 200.  I noticed an immediate reduction (but unfortunately not total disappearance) of cramps and tiredness, and hope you have similar benefits.  I'm now on 4-monthly check-ups (next one in a couple of weeks), which also helps.

Olivia

So 3 weeks into the reduced dose, it is a bit early to know much - my first blood test is 10 days away. However I've not had a significant attack of cramp, and the flatulence issue seems to be reduced. It hasn't helped that I started a cold at the same time as reducing the dose, and that lasted 10 days. Out walking the dog today, my wife commented I was walking faster than usual, and I walked straight up a hill where I have needed a rest half way up every time since we started doing this walk last year. Hadn't anticipated that impact, and makes it even more worth trying. 

Hi Chrissie

No, I'm back up to 300 mg as my last couple of PCRs showed a slight rise.  I don't notice much difference in side effects, though I did have an eye bleed - very unusually for me - almost as soon as I went back to 300.  Perhaps I can get back down again some time, I just hope I don't have to go back to 400 mg.

Thanks for asking!

Olivia

Fantastic news for you. You must be delighted.

Are you planning on dropping lower than 200mg any time soon?

Thank you very much for sharing your results.  We are baby steps into Imatinib and we find this so encouaging that it can be done.  We are having issues with side effects but still hoping that we don't have to change to another TKI.  We will find out next week with our 3 months BCR-ABL1 results.   A lower dosage sounds wonderful so congratulations.

Would you mind sharing with me when you started Imatinib? 

Thanks, and all the best.

Tim and Michelle

Alastair, thanks for keeping us updated as to your PCR results now you are on a reduced dose of IM. The rational behind the Destiny protocol differed from other stopping trials - e.g. STIM, Euroski -

by including a de-escalation (dose reduction) phase in the first year. The thinking behind this was, and still is, that most CML patients who respond well to TKI therapy (with molecular responses at 0.1% -MR3 - or lower) over the first few years of therapy, will be able to maintain a molecular response in spite of a dose reduction.

If most 'good responders' can successfully halve the recommended dose with out losing MR3 (0,1%), then there is now good evidence that side effects are diminished, with an improvement in quality of life.

DESTINY has had excellent results and It seems has proved that although the percentage of patients eligible to stop and achieve TFR is very small (between 15-20% of good responders), dose reduction represents a pragmatic and positive approach towards dealing with TKI side effects for the majority of patients who will need to continue with therapy over the longer term. 

Wishing you well, and hope you will continue to maintain your MR over the coming months.

Best wishes,

Sandy

Hi folks, just back from the latest appointment at the hospital, now approaching 6 months into reduction from 400mg Imatinib to 200 mg.

BCR ABL Results

Dec 0.000%

Jan 0.000%

Feb 0.005%

Prof Clarke's protocol from the trial says don't worry as long as results are less than 0.1%. So still a factor of 20 below any need to go back to 400mg. Was at a friend's 60th birthday party last week and danced till 2 a.m. Not sure I could have done that this time last year.

Best wishes to all.

Good news Alastair. 

I think dose reduction is shaping up to be the way to go for the majority of patients who have deep and stable PCR results. As you know L'pool has a lab with a sensitive PCR methodology, so the odd BCR/ABL1 transcript or two is probably insignificant. As you may or may not know, my PCR results were negative (0.00%) for some years post transplant... then when HH Lab set in place a more sensitive PCR test, suddenly I started seeing results with low positive transcripts. This has remained the case for the last 4 or so years with my results always stable at 0.002% - sometimes 0.001%. this number is very difficult to quantify, so I pay it no mind as it remains is a stable result. 

I wish you well with your half dose regime - who knows you might be able to reduce even further. To me, low dose TKI treatment, wherever possible, is a far more realistic proposition than TFR for a majority with stable MR..... with dose reduction It seems that you can remain stable at MR3 (0.1%) or lower which means many more people (who are not good candidates for TFR) will be able to reduce their side effects and have a much better quality of life in the longer term.

In my view, until we understand the mechanisms behind why a minority of patients with stable deep molecular response (DMR) are able to stop therapy without losing their MR, dose reduction is a much more realistic goal. 

Sandy

Hi  Alastair,i   have been on 400 imatinib for a year + RECENTLY gone down to 300 as I find great difficultly sleeping  , has anyone else had this trouble do you know,  also joint pain , listless, + exhausted.

I was looking for info on the cml  trial but can't find anything. 

 Regards  Dawn

Hi Dawn & Justine.

Sandy knows more than I do but I can say the trials on dose reduction were based on people who had been taking imatinib longer than it seems you both have been. In around 1 year getting to below 0.1% BCR ABL or close to it is a good result, and most people I'm aware of who have reduced dose stabilised at those low levels for several years before trying to reduce. There is research which shows that different people on imatinib have large variations in blood concentration of the drug, for reasons we don't fully understand. For those who get a high blood level, dose reduction may be a good option. If you are having bad side effects you can ask your consultant to check your blood or serum level. Kings College developed a new way of doing this test a few years ago, but it is not widely used. I have posted a link on here before; if you can't find it let me know and I'll look it up.

Hope this helps

Alastair 

Dear Alistair,

Thank you for your reply .I am in Nottingham + go to City hospital next week for bloods ect.  will try to speak to doc then . I could cope with the days if I could sleep at night. my gp  says he can't help me  that any sleeping tabs. are addictive + don.t work for very long.

Feeling  fed up ................  but 11 years + counting .  They gave me 2 weeks   gp  wouldn't listen to me  he thought my husband was beating me !   Anyway thankyou for being there for me.     Dawn

Congrats on your reduction, I have a question I to have been reduced to 200mg of gleevec and have noticed a slight elevation in creatinine clearance in the blood tests, did you have any issues with changes in other blood tests when you dosage was lowered. I had been on gleevec 400mg for 7 years prior to being reduced and Bcr test has shown a slight increase over the last 6 months from 0.00% to 0.03%

All, just back from my appointment, 9 months after reducing from 400mg Imatinib to 200mg.

BCR-ABL Results

March 0.000%

April 0.001%

May 0.000%

So happily maintaining PCRU on 200mg. Appointment at end September and if this continues I will stop taking Imatinib and see if I am one of the lucky ones who can get to TFR.

Consultant was at a conference last week where he said there was an emerging consensus that dose reduction on TKIs and TFR was more likely to be successful the longer the patient has been in MMR.

Rich, sorry I forgot to look at the creatinine numbers!

So another visit to consultant today. PCR 0.002% on 200mg. I will continue to take 200mg imatinib for another 2-3 weeks until today's PCR result is back, and if still stable, I will stop taking imatinib and see if I am one of the lucky 70% who can acheive TFR. 

A (nowadays) rare post from me but this question and my recent PCR result (the two things are unconnected!) have prompted me to do so.

First, I didn't have the latest PCR result at the patient day in Birmingham - when I spoke, I mentioned that I'd had a few very small positives after going on DESTINY and beyond.  Well, the most recent PCR (early September) is once again 0.000 - so recorded as "undetectable".  This does rather suggest that the few small positives I've had in the past 3-4 years are probably not real (the highest number on the IS was 0.002% and my consultant suspects all the positives were probably artefact from the lab, not transcripts in my blood). I suspect she is right. Anyway, three years after stopping I appear still to be "undetectable".

Secondly, I now recall where I first saw the question of renal function, creatinine levels and imatinib. It must have been this post - mild impact on renal function of imatninib was also mentioned at the patient day as a potential side effect.  My creatinine certainly went up on imatinib, and my renal function numbers indicated mild chronic kidney disease CKD.  Indeed, I was investigated for this but it wasn't getting any worse so they decided it was all stable.  This was at a time before imatinib effects on renal function had been discussed (no one mentioned them to me).  

As I mentioned at the patient day, my renal function is now completely normal - creatinine levels are back where they should be.  I strongly suspect this is because I have stopped imatinib.  My experience supports a mild effect on kidney function of imatinib but one which reverses and indeed in any event seems to be pretty minor.  This is purely anecdotal and I mention it simply for the information of others. I've never discussed this with my consultant at the Hammersmith (it was another hospital that picked it up, when I had joint care).

Richard

Hi everyone. Today is the first day in 11.5 years that I deliberately won't take any pills. 12 months on 200mg imatinib has passed uneventfully, highest PCR was 0.005%, so negligible. Next test is on 22 November, it will be interesting to see if I can stay at that level. Prof Clarke's data from Destiny showed that if the counts start going back up months 3-6 is the most likely time, so we will watch and hope, and see what other impacts (withdrawal symptoms or reduced side effects) arise. 

Fingers crossed.

Best of luck Alastair! It must be a strange but exciting feeling!

Thanks to all for good wishes. Chrissie, I had not thought about the grapefruit question! 

Totally.  Miss grapefruit tremendously!

Hi everyone. Delighted to say my PCR from mid November is confirmed as 0.000% (7 weeks post stopping taking the pills). I knew it would be as the deal I have with my consultant is that I see him every two months and if the PCR result comes back and is not comfortably maintaining MMR he will contact me. Still feeling fine, no cramp, reduced flatulence and no "out of petrol" days in the last couple of months.

Interesting chat - he has some patients who don't want to consider dose reduction as they think he only suggests it to save the NHS money! The increased number of PCR tests costs more early on than the saving on generic imatinib. Also  discussed how quickly patients who achieve MMR should start thinking about dose reduction and trying for TFR. Several years gives the best chance of success - evidence suggests ideally 5 years.

Congratulations Alistair for TFR.....

YOUR PCR TEST...... EVERY MONTH / EVERY TWO MONTH /THREE....???

Just for information, when DESTINY ended for me (and I was still 0.000), I went to three monthly appointments. That was in May 2017.  I went to four monthly appointments in May 2018. Awaiting my latest PCR (sample taken last week so won't have the result for a couple of weeks from now I think - I expect it to be 0.000 or a small - probably false - positive eg 0.002). 

Hospital comfortable with this regime given that I've been essentially 0.000 since November 2009 and have been in TFR since May 2015 (ie when the DESTINY protocol meant I stopped imatinib completely).

Richard

Visit to clinic today PCR 0.03% from my test in January, which is the highest result I had during the half dose regime, which then returned to 0.000 six weeks later. Sticking with the Destiny protocol of ignoring any result below 0.1%; next test in June. My deal with my consultant is he will contact me if the test taken today gives a result over 0.1%. Now over 4 months into stopping imatinib. Onward.

Great news Alastair. I am currently awaiting my first results after dropping to 200 mgs imainib in Jan 2019. Hope to be as lucky as you. Keep on posting,

Best

Chrissie

That's awesome! Cheering for continued success : )