Appointment this week at Countess of Chester Hospital, where the (new) consultant has agreed to follow Prof Clarke's proposed protocol that we cut my imatinib from 400mg to 200mg. I will have monthly BCR-ABL to check for any progression, and see them again at CoC just before Christmas. My PCR-ABl has been undetectable since 2009. If it stays at zero for a year on 200mg we will then stop. I will keep the forum posted on progress.
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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
Good luck Alastair - DESTINY results so far are cause for optimism that you will succeed in both dose reduction and then going off completely. I have also been undetectable since late 2009 and went on Destiny in 2014. I finished Destiny in May - had a couple of blips in the results at one stage (which turned out not to be real) but other than that, with monthly testing for the first two years, then two monthly, I felt in safe hands. Reducing to 200mg immediately reduced side effects to more or less nothing. Richard
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.
I, too, am on the reduced dose of Imatinib down from 400 to 300 mgs - and what a difference. I had a weight problem in that it just refused to budge despite gym, swimming walking,fitness classes etc etc. Now it's shifting. More energy, less puffing when walking up one of the many Devon hills around here. I went onto 300mgs in June and am still holding MR4 so pleased after my DESTINY failure on half dose.
Are you still holding remission on 200mgs, Olivia?
Best
Chrissie
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
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
Thanks for all good wishes.
David, the plan is to stay on 200mg for a total of 12 months (i.e. another 8 from now). Prof Clarke's protocol says to ignore any results less than 0.1% through this period. If all is good I will stop in September and continue to be tested monthly for the first 6 months.
Tim and Michelle, I started taking imatinib in the spring of 2007. Initially 400mg, but I have always had a very low wbc ( as I detailed on another thread recently) and I went down to 200 mg at the end of 2007 for about 6 months. PCR progress stalled so went back to 400mg and achieved log 3 in 18 months, and undetectable 3 months later.
Alastair
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
Alastair,
Best of Luck on your dosage reduction
My own CML history
02/2010 Gleevec 400mg
2011 Two weakly positives, PCRU, weakly positive
2012 PCRU, PCRU, PCRU, PCRU
2013 PCRU, PCRU, PCRU, weakly positive
2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR
2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000
2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17
In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.
longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation. GFR and creatinine vastly improved after stopping Gleevec.
Cumulative Gleevec dosage estimated at 830 grams
Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.
Buzz
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.
Smashing results!
I'm always slightly wary of a 0.000% ... could just mean the test was poor, and not very specific. Whereas a really low, but positive PCR strangely gives me more comfort in some ways. I once got a 0.000% but it was from 0.02 just before, and 0.02 immediately after. I suspect a clerical error and it was someone else's blood!
David.
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
Dawn, I have also been on Imatinib 400 for a year, began the day of my presumed diagnosis on April 7, 2017. Diagnosis was confirmed within a week or so after PCR test. My WBC was 280K so it was good that I got started right away from an inventory at our hospital pharmacy. I do share all those side effects you mention. It seems that I am able to sleep during the day by napping but not so well at night! Doctor recommends staying as active as I can and also yoga for the joint pain. I enjoy hiking but it does seem to take longer (several days) to recover from anything strenuous. (I am 55.) Yoga does seem to help, for both body and mind. Waiting for my 12 mo. PCR results any day now. Have not talked with doctor about reducing dose but I will ask at next visit in 3 months. Do you feel better on 300? Thank you and good luck. Justine
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
Dawn I've just read your reply to the thread on the conference and it sounds like you need to change something. Assuming you are UK based I suggest you ask your consultant to get your blood imatinib levels checked.Details of a test offered to NHS hospitals through King's College are on this link One of the tabs in the middle of the page gives a link to the request form. There was research published last year that shows that women seem to have a higher serum level of imatinib than men.There are reasons for this which are too complex for me to explain (and I have run a toxicology lab). If the side effects from imatinib are so severe and the level isn't too high perhaps a change of drug might be the way forward.
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
Hi Dawn, good luck with the hospital. I think I've picked up something wrong about your CML journey - you've said 11 years and counting in this post, but above you said 400mg Imatinib for a year, which I though was when you were diagnosed. If you want to share your treatment history and current PCR level it might help people understand and share relevant experience.
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%
Hi Rich
I've not had any issues with other tests since I reduced, but I haven't looked at the creatinine numbers. I'm now seeing the registrar - I am threatening to send my consultant an invoice for training his staff on CML - but will have a look when I go back to see them next month. The consultant is still looking at the numbers, and if I wanted to see him or the results were gong the wrong way I would be seeing him very quickly. I will look at the creatinine numbers next month at my appointment and let you know if there is any change.
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!
This is terrific! Even if TFR isn't ultimately the result, to prove (at least for yet one more person) that reducing a TKI by half can still maintain an extremely low and safe level is AWESOME for all of us!
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
I found the references: TKIs Have Kidney Effects in Long-Term CML Treatment, by the network staff of Cancer magazine, July 31, 2015; and Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia, by Vidal-Petiot et al, in Clinical Lymphoma, Myeloma and Leukemia, March 2016.
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.
Lots of luck with the next test, Alistair. I am watching/reading your account with interest as in Jan 2019 I will start the process, having held at MR4/4.5 on 300mgs since Feb 2016 - 200mgs for one year from Jan and then if still down at MR4/4,5 TF. My haem favours a more gently reduction to avoid withdrawal - hence the extra time on 200mgs.
I bet it seemed very odd not to have to take the tablet on the first few days. I know if I get that far I will be relishing my first grapefruit in over 10 years!
Looking forward to your posting after your next test,
best,
Chrissie
I've not tried grapefruit in the two weeks since I stopped my imatinib - I almost feel guilty given how much some of you are missing it while on your TKIs.
However I can report that despite a fairly strenuous three hour hike, with a good bit of uphill and eleven stiles, I have still not had an incident of cramp since my final dose. That's a significant change for me. First PCR sample will be taken next week.
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.
Fantastic! Great to hear it’s staying stable, and even better that you are feeling better for it.
I have just reduced my dasatinib dose to 20mg, and hoping to see some benefit from that. I could do with all the extra energy I can get at the moment. I’m on 6-weekly PCR tests, but the economics of PCR vs drug is different with dasatinib.
David.
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.
Just back from seeing the consultant. PCR 0.013% at March appointment nearly 6 months after stopping imatinib, having been 0.03% in January . WBC and neutrophil numbers stable and at and at top end of my range. All good.
Great news, Alistair. Still holding MMR after the magic 6 months. I went down to half dosage (200mgs imatinib) in Jan 2019 and mine are slowly rising
Dec 2018 - 0.0049
Feb 2019 - 0.0071
Apr 2019 - 0.0085
Awaiting the next result from bloods taken at GPs May 20th. Am currently being tested every 6 weeks.
The rises above are all very minimal but this may well indicate an upward trend. I am not changing anything until I lose MMR and reach 0.1. When I went down to 300mgs from 400mgs the same thing happened and I had a warning from the genetics lab that a trend had been noted but I hung on with the lower dose (with my haem's support)and regained MR4 so am following the same strategy for now.
Best to everyone,
Chrissiex
Hi, I've only just discovered this forum and read with interest your posts so thanks for sharing. I was diagnosed in 2010, started a full dose of Imatinib until 2015, then went onto the half dose on the Destiny trial and came off completely in May 2016. The levels were barely traceable in the first 2 years but in the last 12 months have been creeping up and as of last week went to 0.17 which unfortunately means I am due to start a full dose again this week. Hugely disappointed but from stats it appears the levels should drop back almost immediately which I hope for but its the side effects that fill me with horror, both physically and mentally. I've lost weight and focused on my fitness in the last 3+ years (regular running, 10k and 1/2 marathons) so I'm hoping my body can deal with the side effects better. I'm told by my Consultant that as I'm no longer part of Destiny or any trial treatment becomes a bespoke process of 'seeing what works' and I'm hoping to go to a half dose quickly - fingers crossed!
Good luck to all and great to read your stories and experiences.
Well I just got my results from May 20th and yep I am now on 0.03% so still in MMR but no longer MR4. We have decided to hang in there on 200mgs and see what happens in the next few months - but I think I may well end up on full dosage once more. The same thing happened with DESTINY back in 2015.Disappointing, but hey I am still alive with a good quality of life and very little in the side effects department. Will post again with June's result once I get them.
Congrats to you lucky few in TFR,
Best
Chrissiex
Chrissie - consider switching drugs if you have to go back. Low dose dasatinib is a good alternative (i.e. < 40 mg).
Data suggests that rotating TKI drugs may do more to increase TFR success than staying on the same drug. Dasatinib works very differently than imatinib and will likely attack the resistant CML.
Just a thought.
Another visit to the clinic today. June BCR-ABL 0.02% - all other results fine (for me - I am still neutropenic, but in the range I have been for 30+ years). Consultant happy that all is stable; he will call me if there is an issue with the BCR-ABL taken today, but the next appointment is in 3 months, which will be 13 months since I last took imatinib.
Hi Vikram, not quite one year yet - 10 months and counting. No issues at all. I had lost the side effects when I reduced from 400mg imatinib to 200mg. That felt like a much bigger change than going from 200mg to zero.
I’m currently on imatinib for the past 8 years. Over the past year and a half been reduced from 400 mg to 200 mg. My bcr/abl has been at a 3 log reduction for the entirety of usage of imatinib and still holding strong according to my last test in July. My question is did your doctor recommend stopping medication completely due to side effects or to see if numbers were stable enough to start clinical trial for zero usage? Just wondering because I’ve actually noticed more side effects with the reduction from 400 mg to 200mg. Congrats by the way with being off the meds completely, gives me hope that one day I might not have to take medications anymore
Hi,
In answer to your best wishes, here are my results after dropping from 300 to 200mgs imatinib with the hope of stopping in Jan 2020. From July 2017 when I dropped to 300mgs from 400mgs I was holding happily at MR4, bouncing around a bit between 0.008-0.001. This led myself and my haem to drop again to 200mgs in Jan 2019 - and since then my results were taken every 6 weeks as follows:
Dec 2018 - 0.004
Feb 2019- 0.007
Apr 2019 - 0.008
May 2019 - 0.03
July 2019 - 0.05
Now my options were: 1) carry on taking 200mgs and hope the immune system ( + daily brazil nuts!) wakes up and takes over knocking the "nasties" back down again OR 2) go immediately onto the full 400mgs as when I lost MMR on DESTINY in 2015 - although I hadn't lost MMR yet OR 3) go back to 300mgs and see what happens.
My haem left it down to me and I decided, as the 300mgs gave me no side effects, to return to 300mgs which I did on July 23 . I wanted to avoid having all the side effects again after so long off the full dose.Now awaiting the first blood test results since I started on 300mgs- but only 3 weeks of taking 300mgs so not holding my breath.
Half of me thinks I should have waited till I lost MMR before increasing the dose and the other half tells me I really wouldn't want the puffy, watery eyes, cramps etc again. Just hope the 300mgs does the trick.
Best to all
Chrissie
Hi everyone
Ray I was on imatinib at 400mg for over 10 years. Reduced to 200mg in October 2017, and stayed at around .005%. Stopped end of October last year.
Rich I am following the protocol of the Destiny Trial. I wanted to try reducing and potentially stopping to get away from side effects (flatulence, cramps, fatigue etc.) There are papers on e the site which show the results. The reduction to 200mg got rid of most of the side effects; it had a bigger effect than going from 200mg to zero.
Chrissie I'm entirely with you. I'd like to get back below .01%, and will look at supplementing to see if it helps. My consultant is happy that I'm stable at around 0.02%, but I'd like that second zero back. If it drifts up I will be more likely to want to start back on 200mg because the side effects at 400mg were much more significant. Waiting to lose MMR and then going back to 400mg is not where I want to be.
Hi
Just to let you know that after returning to 300mgs imatinib on July 23 my first test showed a very marginal drop form 0.05% to 0.04%. Yes I know no difference there but it's the first test with results that have gone down/stayed the same sine Jan when I went onto 200mgs and got steady rises ( the dreaded trend!) every 6 weeks. Next blood test Oct 14th so hoping to see more of a drop so I can stay on 300mgs rather than the full dose.
Best, Chrissie
Hi everyone,
Just though I should mark that it is 12 months today since I stopped taking imatinib. PCR stable around 0.02%. I'd be happier to get the second zero back if that is possible. As I said on another thread the reduction in side effects from 400mg to 200mg was more significant to me than the reduction from 200mg to zero. I do have more energy in the last year, and less brain fog, but that has been gradual over the year. I have not had any usual cramp, no eye bleeds and fluid retention has decreased. Next test on Nov 13th. Onwards.
That’s fab. Congratulations.
I don’t know the number off hand, but doesn’t DENTINY have some predictive data around if you stay in MMR for x period of time, you are more than likely to remain in TFR?
David.
David, thanks for motivating me to watch the video of Prof Clark's talk at the Patient Day in Leeds. Of the patients who started Destiny in MR4 or better (like me), about 72% were still in MMR or better 24 months into the trial, which was 12 months after stopping. In the next year less than 5% more lost MMR, so my odds are looking pretty optimistic. Important to note that ALL who lost MMR regained it when they started taking the meds again.
They have also done some more modelling on the data which is really interesting. During the half dose stage in the first 12 months, most people's PCRs moved a round a bit. For those who over the period the movement was random, there was a good likelihood of cessation working. If there was a small but noticeable overall upward trend over the 12 months, cessation was much less likely to be successful. Early days for this yet, but a clear indication for those considering TFR. Try half dose, and plot your PCRs. If the best fit line through all the points has a slope of zero, TFR is well worth trying. If there is a small positive slope it may well be best stay on half dose as TFR is less likely to work for you.
Hi there
Just had my second result since restarting 300mgs Imatinib after my results showed a slow and steady rise from MR4 over 7 months on 200mgs reaching 0,05% in July which caused me to decide to rerurn to 300mgs instead of waiting to lose MMR and then maybe having to go back to full dose.. First result on 300mgs was 0.04%, the latest is 0.01% so obvously 300mgs is "my" dose. No side effets to speak of.
Hope all those on TFR can carry on - envious of the grapefruit!!
best
Chrissie
Just had a call from the consultant. My August test did not give a result, and no-one noticed and asked me to go back for another sample, which is far from good. My test in mid-November was therefore the first for 5 months. 0.02% again, so I am now stable at that level for 6 months. Now over 13 months since I took my last imatinib. I think this what TFR feels like.
Hi David, I lost most of the side effects when I dropped to 200mg from 400mg. Since stopping I definitely have more energy, and don't have brain fogged days any more. (Slight fog this morning is down to a couple of extra glasses of mulled wine after the carol concert last night,partly as a TFR celebration ). I'd become a bit sedentary other than walking the dog; have started doing Pilates in the last few months which is improving core strength and flexibility. Don't think I'd have had the drive to make myself do that while still on imatinib.
Hi Vikram, yes still in TFR as far as I know 0.018% PCR. Next test due middle of May, but not sure how things will be at the hospital by then. I would not be surprised or worried if they ask me not to come.
Just to keep this thread complete PCR 0.01% from test in February this year. New sample taken yesterday - briefly in the hospital where several staff were not social distancing as I would have expected. I wore a mask and clothes went straight in the washing machine when I got home. Next appointment arrived in the post for early October, so nearly 5 months. Bears out the consultant's view on phone consultation that my TFR is pretty stable. Assuming his test is OK I will be over 18 months
Unfortunately the TFR journey has come to an end. BCR-ABL 0.15% from the test two weeks ago, so back on to 400mg imatinib. Hopefully get back down to MR4 again quite quickly and reduce to 200mg where the numbers were fine and most of the side effects disappeared. 19 months off the meds have been well worth it.
HI Alistair
Disappointed for you . After 19 months in TFR I thought you would be OK . Just shows how CML can catch up with us . I hope you regain MR4 quickly on 400mgs and the side effects of going back onto meds aren't too bad. We all seem to have our minimum safe dose - yours might be 200mgs once stabilised and I have accepted I can never go TF (eat grapefruit) or even take half dose but am happy on 300mgs and the CML seems to be staying at MR4/MR4.5. Fingers crossed, as I avoided a blood test in April due to Cov with my haem's consent but have one booked for June 22. The GP surgery is sending a district nurse to take bloods at home. All my appts with the haem are phone with bloods taken at GP surgery and have been for a few years now so I can avoid the hospital completely in normal times, let alone now.
Good luck, take care,
Best
Chrissie
Thanks to all for good wishes. Alcura have been very efficient; new supply of Sandoz generics was here at 10.00 this morning, and took the first one after an early lunch.
Denise I didn't think about Dasatinib; the consultant was set on going back to imatinib, and I wasn't ready enough for the discussion. I didn't have as much of an issue with imatinib at 400mg as you did, so I'll see how it goes.
All the best back on 400mg Imatinib - I am just curious though as you have been stable in TFR for a long stretch, did you consider just repeating the test, in case the result was not valid?
Thank you for info. There is some self interest here: I was on 400mg inatinib for 11 years then 200mg for 5 with very low bcr abl but never quite zero. In principle a good candidate for TFR. I stopped imatinib last August and my results have crept up to hover around 0.015. Not tested since march because no clinic but test now next week so I suspect if the creeping has continued I may be back on Imatinib. Never had any real serious side effects but 200mg so much better for energy levels so am tempted to start again with 200. In the meantime will be consuming grapefuit... :)
I absolutely agree with you about the difference between 200 and 400. I had a conversation with my consultant on starting back at 200mg, but as it is not what the protocol says he would not support it. However if I get back to less than 0.01% in say six months we will be having a dose reduction discussion again, and I may well take my own decision, specifically if the side effects are bothering me. (Hope he doesn't read this!) If you think the trend is going up slowly I would encourage you to have the 200mg discussion before you get to 0.1%. Best wishes
HI Alistair,
Would you consider switching to low dose dasatnib? Data is emerging suggesting drug rotation (especially imatinib to dasatnib) helps attack CML more thoroughly than one TKI alone. This may enable you to try cessation again in the future with greater success possibility. Also - low dose dasatnib (i.e. 20 - 40 mg) has fewer side effects. In my case I feel none. And you can take it without food avoiding nausea which is common with imatinib on an empty stomach. You may find low dose dasatnib drops you to <0.01% very fast - perhaps even undetected again. Just a thought.
Hi Scuba
I should have asked the consultant this question when he called but was not ready, so took his advice to stay with the established protocol of 400mg imatinib. If I don't make swift progress back to MR4 so I can go back to 200mg Im , there will be a discussion about dasatinib, and I will be taking some of the data you have posted with me. I have also told him to check my Vit D at the next blood test, in early July. My Vit D should be as good as it has been for a long time right now - have spent a lot of the last 9 weeks of lockdown in the garden, without which it would have been much more difficult.
Thanks
Alastair
Although not specific to your case, interesting application of drug rotation leading a patient from blast crisis to DMR.
These doctors were 'thinking outside of the box' and developed a unique protocol for this one patient in application of "personalized medicine". It worked.
Imatinib and nilotinib, as an aside, work the same way in binding to the ATP side in bcr-abl with nilotinib binding more tightly. But dasatnib, in addition to binding to bcr-abl also binds to other conformations of the ABL kinase domain affecting higher order CML cells. It is intriguing that imatinib and dasatinib together might be a one-two punch you need to provide long lasting TFR. Just a hunch, but intriguing nonetheless. It will be interesting if your doctor is aware of TKI rotation in CML treatment.
(I took imatinib first as most new patients do and wonder even though it failed for me, it might have prepared the way for dasatinib to be more effective.)
Just a quick update after 3 weeks back on 400mg imatinib. I was dreading the bone pain I had when I first started imatinib (in 2007!), but it has not materialised. I've had a bit of gastric rumbling but not a major issue - a digestive biscuit seems to sort that out so not all bad. Also very little cramp, and I've not felt more tired. So really as good as I could have hoped back on the meds after 17 months off.
Dear Ray, I been on glivec for 10 yrs. + put on weight with the water retension + for 4 yrs. on various different makes all with side affects, tabs. change every 3 months. Is everyone else having this trouble/? I went onto 200mg instead of 400 mg because of s, effects. I go to City hospital 3 july, be nice to see a doctor again! But we're still here, Also been on the L. care meetings on pc, interesting. Regards Dawn.
Hi Dawn. I’m now 4 yrs with CML. Started at 600mg imatinib (2 years). Not sure why, no blasts, horrible side effects. Dropped to 400mg on my own. I will re test in Aug. If PCR isn’t significantly down, think I will change meds. Like so many of us, I would ultimately like to get off meds. Regards, Ray
Hi Dawn. I’m now 4 yrs with CML. Started at 600mg imatinib (2 years). Not sure why, no blasts, horrible side effects. Dropped to 400mg on my own. I will re test in Aug. If PCR isn’t significantly down, think I will change meds. Like so many of us, I would ultimately like to get off meds. Regards, Ray
AlastairC. 6 months ago BCR ABL .350
3 months ago BCR ABL .250
New labs Aug 27 Mines going the right
way A real snails pace was lower until lab change then went way up Guess it’s much better lab Thank you Ray
Hi Ray, thanks for the info. If you are having to change test labs please read the page on this link.
Important to try to get comparability of the results of the two labs on the International Scale (IS).
Let's see what the August result is. Keep in touch
Best
Alastair
Why would you like to get off your meds. you have no side affects, Didn't your doctor know you were going to reduce the dose?
Imatinib seems to help me + has kept me clear for 13 yrs. I didn't expect that long really , just kept going!
If this doesn't work for you try another drug at least we have options.
Stay well take care . D
Having gone back onto 400mg Imatinib in early June when BCR-ABL went to 0.154%, I had a another test on 6 July. That result is 0.132%; not a huge reduction but probably going in the right direction. Another test in around about 6 weeks from now, so 2 months from the last one and I hope I'll be back to MMR or better.
AlastairC During your time off Imatinib, did you have any life style changes? Have you ever opened a new prescription of Imatinib and it had a really foul smell? I get 30 day supply and now on Imatinib for 4 years. This has happened to me 3-4 times. So offensive, couple times I just put cap on and didn't take it.
Thank you
Ray
Ray the biggest change for me was when I reduced for 400mg to 200mg. I lost the cramps, much less likely to have gastric upset, and there were many fewer days when I had no energy. Less oedema as well. The TFR attempt was worthwhile, but I hope to get to MR4 quite quickly and when that is stable reduce to 200mg again and stay there.
Never had an issue with smell of imatinib but my sense of smell and taste are not as sensitive as many people. My current supply is Sandoz, but had no issues when I was taking Wockhardt a few years ago.
3 months after starting back on 400mg imatinib after my 17 months TFR attempt, and I am back at BCR-ABL 0.001%. We will make sure this is stable over the next months, and consultant has agreed that if it is maintained we can discuss going back to 200mg some time in the middle of next year. Having a bit more cramp and gastric gurgling than I would like but not too bad.
Congratulations on such a quick and deep response. What is reason for waiting 8 months for reduction of imatinib? I’m just curious as you’ve had so much success. Thank you Ray
Well done Alistair. My first test 26 days after restarting 150 mg Tasigna was unchanged at .02%. Better than continuing to go up, but I had hoped for some reduction. Hopefully that will happen at next month's test.
Hi Blood test taken 29 November has returned 0.000%. So back to 400mg imatinib has got me back to PCRU in 5 months from when I failed to maintain TFR after 19 months. Actually probably quicker because the previous test did not give a result. Next blood sample 1 February - if that is maintained we will have a discussion about 200mg.
We also talked about covid immunisation - his message was simple - when they call you - go.
Man I’m glad to hear of your results
We are all so different and reactions to the CML drugs is incredible Amazing difference in doctors as well My Dr said last week she was taking COVID vaccine as she’s first liner. She’s advising her parents to wait 6 months as this is first time of this type of drug ever produced. I’m more cautious
Hello Alistair
I have read this post from start to finish, following your progress. Congratulations on your latest blood test result, such good news.
Interesting to hear about your, and everybody else’s side effects. The drug certainly seems to affect people differently. I have been suffering with slight joint/bone(?) pain, tiredness and light headedness, with occasional light headaches. My blood pressure (particularly the diastolic) has raised suddenly, after a lifetime of good blood pressure. I wonder if this could be a side effect of Imatinib??
Sadly as I am very much a beginner (6 weeks on Imatinib) I have a long way to go before getting to your exalted stage!
The call came from the health centre last week, much to my surprise, so I “bit their arm off” and had the first of my COVID-19 vaccinations.
Best wishes
David
Hi Alastair
Great news on your latest bloods. I too, after 11+ years and on 300mgs imatinib finally got 0.0000% in June 2020, 0.002% in Sept and 0.0000 again end Nov. Another 2 years and I shall try TF although my record at attempting 200mgs didn't keep it down in the 2 occasions I tried so I shall see.
Best Christmas wishes to everyone and bring on 2021 and the vaccine.
Best
Chrissie
Thanks Chrissie and I'm delighted to hear about your zeros too.
As far as try TFR is concerned have you listened to Prof Clark's talk at the patient conference last year in Leeds? It is on this link quite far down. He talks about trends while on the half dose in Destiny being good indicators as to whether TFR is likely to be achievable. Hope this is useful.
Have a great Christmas and stay safe.
Alastair
Thanks for the link, Alistair. I have watched Prof Clark's talk. Yes it was on DESTINY that my 200mgs failed in Month 13 probably as I was only in MMR when I started the trial. I tried 200mgs again in Jan 2019 think when I was at MR4 on 300mgs and lost MR4 in the summer. Back onto 300mgs at 0.05% ( yes still in MMR but I wanted to avoid 400mgs). regained MR4 quickly and in June 2020 got my first undetectable which has been repeated in Nov. i ma probbal ynot acandidate for treatment free but afte ra few years I may well try to see.
Seasonal best wishes,
Chrissie
Hi Vikram
Currently on 400mg imatinib. Undetectable from test on 1 December; had a sample taken last week will get results on 24 Feb.
Hope you are still doing well
Alastair
Alastair, how long do they require you to be undetectable again before they permit you to lower your dosage? and then will it be lowered to 200mg? In that you held TFR for a lengthy period it shouldn't require much in the way of a maintenance dose to control your CML. 100mg is likely a given; 50mg a high probability. Gradual dosage reduction.
Discussion today with consultant on a PCR undetectable result from a test early this month. He wasn't willing to look at dose reduction now; wants to see a full year on 400mg. When we talk again in May after a test in late April we will consider a reduction to 200mg. He is going to ask around on any experience in his network on that; if anyone who has tried and lost TFR, gone back to full dose and then reduced again, I'd really like to hear from you.
HI Alistair,
Dx in Sept 2009. Not tried TFR yet but have reduced to 200mgs imatinib twice - and failed both times.
First on DESTINY in 2014/15 but only in MMR. Lost MMR in month 13 (up to 0.5%) so back onto 400mgs after haem phoned me at 9pm one evening.
Regained MMR , down to MR4 so went onto 300mgs July 2017, looked good, held MR4 so down to 200mgs Feb 2019.
July 2nd 2019 PCR rose to 0.05% - still MMR but I didn't want it to rise any higher so I would have to go onto 400mgs so I went back onto 300mgs. reached 0.0000% (MR5) June 2020 and have held it - still on 300mgs. Thinking of maybe trying TFR 2022/ 23 sometime if I am still undetectable.
Hope it helps - but my case certainly shows how
1) we can regain MMR after trying to reduce and
2) we all have out optimal doses ( mine is 300mgs) and can still reach "undetectable" on that.
3) To ensure BCR ABL is very low for a number of years before trying. I think the DESTINY results also show we need to be at the most MR4 stable or MR4.5 for a few years.
Best
Chrissie
Hi Alistair,
Thanks for sharing your story. It is really gives hope and strengths to us.
I was diagnosed in 2008 was on 400mg imatinib (Glivec) and after 8 years of treatment I decided to stop and succeeded to be TFR for two years till the numbers started to rise up.
In 2018 I went back to generic imatinib 400mg (Teva). Surprisly, It was with less side effects. And in the last two years I'm undetectable or less than MR4.5.
I would like to reduce dose to 300mg but my doctor thinks that I should stay on 400mg as long as everything is working.
How was the change from 400mg (1 pill) to (300mg (3 pills) for you?
Thanks again for sharing.
I wish to you and to all of us to be TFR at least until CML cure is found.
Best regards and stay safe and 💪
Gil Vivante
Hi Gil, thanks for this. I did a year at 200mg before I stopped completely. At 200mg the side effects (cramp, water retention, flatulence) reduced significantly, and I held MR4.5. That suggests if I go back to 200mg now I'll be fine again. I also found that when I went back to 400mg that the side effescts were not as bad as they were first time round. I think there is a good chance you might do well on a smaller dose.
Thanks Chrissie - more useful data. In cases like yours I wonder why the doctors don't use the available test to look at the plasma/serum concentrations in our blood. Work at Kings some years ago showed that the standard 400mg dose gave a very wide range of concentrations in different patients. Thus to me if you check that you can adjust the dose so that the therapeutic level is achieved in blood without (in some cases) horrendous side effects in those who get the highest blood levels. However I think you have found your dose level.
Buzz if you know of any published study on using dosages of less than 200mg imatinib please can you point me to it? Thanks
Another 0.000% BCR-ABL result today. Consultant is taking my case history to a meeting of specialists being convened by Prof Copeland at Glasgow to discuss going back to 200mg. I will hear outcome in early July.
My consultant has agreed that I can return to 200 mg of imatinib. Before I do that he wants another BCR-ABL test, and for us both to confirm the result before I make the change. So bloods next week and once I have the result I will be back on 200mg. I was a flat line 0.000 on 200mg with one exception in 2017/18 before I tried TFR, and hope to be the same again.
After some issues getting a valid BCRABL (described on another thread), based on another 0.000 my consultant has today agreed to reduce my imatinib dose to 200mg. I am confident that I will hold PCRU on that level. Next test mid December.
Hi All
As recorded on another thread I had 4 weeks off my 200mg imatinib while a wound healed after hip replacement surgery in late July. Went back on 200mg in late August, and BCRABL undetectable in a blood sample taken 8 December. Moving to a blood test every 4 months.
Hola Alaister.
Que bueno que estés bien , gracias por mantenernos informados. Dios mediante algún momento dejaras de tomar imatinib por completo. Yo recién tengo 2 meses tomando imatinib de 400 mg , pero me siento bastante bien. En febrero tengo mi cita médica para control .
Saludos y bendiciones
Hola
I tried TFR a few years ago. I reduced from 400mg imatinib to 200 for a year, and then stopped. I did not take any imatinib for 17 months, but my BCRABL eventually rose above 0.1, so I went back onto 400mg. Once the BCRABL was stable below 0.01, I reduced back to 200mg. I have very few side effects on 200mg, so will likely not try TFR again.
Just to keep the history going, I've had another undetectable BCRABL result today. That's 2 years after going back to 200mg imatinib, after a year at 400mg after losing TFR. Side effects minimal. All good.
Vikram any BCR ABL result less than 0.01 is likely an effect of he test process and is effectively an undetectable, so I would not worry. It may be that your lab has an ew, more sensitive test machine which has given this answer which is within the +/- variability of the test process. I would only consider a dose increase if three consecutive tests showed an increase in BCRABL towards 0.1 %
CBC report
Hemoglobin: 16.2
Total RBC Count : 6.09
Total WBC Count : 14260 [range 4000-11000]
Platelet Count: 582000 [range 1,00,000-4,50,000]
Wbc and platelet? High .... dengerus?
Hi Alastair,
A couple of days ago I stumbled on the paper below about Imatinib not being able to reach CML cells in the central nervous system from where they tend to relapse following the discontinuation of treatment. It’s from 2007 so I‘m not sure if it’s still valid/true, but thought you may want to discuss it with your doctor re potential TFR.
Imatinib-resistant chronic myeloid leukemia (CML): Current concepts on pathogenesis and new emerging pharmacologic approaches
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721289/
Zoran
Zoran at this stage I'm not planning another TFR attempt thanks.
I actually saw my consultant yesterday - first time for over 3 years as we have had a routine of him calling me with blood test results. The numbers are fine, and we will revert to the blood test/phone call routine (3 times/year) and a face to face every couple of years.