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Question for dose reduction/ TFR folk

Hi all,

I've been on imatanib 400mg daily for a few years. Ive been having energy and brain fog issues recently and ive always background wondered if i could maintain my response with a lower dose.

So far i have not found any specialist that is willing to consider a dose reduction protocol (ive been followed in Switzerland and UAE). I know the UK seem to lead the way with this.

I have decent flexible health insurance and may be free to work from anywhere later this year. Im asking for recommendations for specific specialists in Europe who are willing to explore dose reduction/TFR options with me and are experienced with the protocol.

I would like to work with a doctor who is in favour of dose reduction as i believe the physicians attitude is important.

Some further info:

Dx in june 2016
Full MMR Feb 2017, which has maintained ever since

EvaH, I'm a strong advocate of TKI dosage reduction as early as possible dependent on response.  Five years ia a very long time to be on full dosage of any TKI; the risk of damage from the TKI, at full dosage, increases with time.

It would help to better understand your situation if you post your CML chronological history; please include test dates and results.

Thanks in advance,
Buzz

Hi Eva,

Any particular part of Europe? I recall you may have been treated in Switzerland before, is that right? Andreas Hochhaus has done a fair bit around dose reduction studies. He's in Jena, Germany. No idea if he takes private patients from outside Germany though (and in general I am not familiar with how the German healthcare system works).

David.

Not really, I'm in the Middle East at the moment. But i doubt ill find some one here.

I have family in Uk so that's an option, though i would prefer to be based somewhere with better weather and cheaper than London :)

The idea would be to plan to spend some time (6-12 months) somewhere i can work with a specialist who is experienced and pro dose reduction.

I like my hematologist but he is old enough to have seen most of his patients die and for him the risk of tfr doesn't outweigh the benefits. That's fair enough, and he is over the usual retirement age so i doubt ill change his mind. I also saw this attitude in Switzerland, likely due to the high levels of private insurance in both countries as opposed to nationalised medical in uk and Germany

Hi Buzz

I assume you are looking for my WBC and MMR between june 2016 and Feb 2017? MMR & FBC totally normal since feb 2017

I had 330,000 wbc and 2 million platlets on diagnosis and returned to normal blood parameters (hematological response by Aug/Sept 2016). Suboptimal bcr/abl response at 3 months but within good parameters by month 6.

If you let me know exactly what you like to see , I'll dig out the data.

EvaH, I am interested in your BCR-ABL readings 2016-2021.  Thanks!

June 2016 assumed 100%

Early August 2016 39%

Mid Oct 2016 13%

Late Dec 2016 4%

Early Feb 0.04%

Since then till now - undetectable

 

You can see it on this graph (hopefully )

https://drive.google.com/drive/u/0/folders/0B1ZBE6ZEDbHgU2gyX1RyY3RoZG8

EvaH, you have been undetectable for four years.  You are in a position to either attempt TFR immediately, or to begin reducing your dosage immediately, leading to a TFR attempt; your choice.  I am very surprised that your oncologist, or any others that you may have consulted, haven't broached the subject.   

There are benefits in first reducing your dosage to as low as possible before attempting TFR, in that should you fail TFR, you can justifiably argue to restart at a lower dosage, rather than the full dosage that most oncs still insist on.

You might want to read my thoughts on the subject:
https://communityview.lls.org/users/buzzm1
if you scroll down, the Stop Studies are summarized
 

 

Thanks for the article and confirming my suspicions.

I have brought up the subject with oncologists in both countries where I've been treated. None were interested because for them the possibility of relapse isn't worth it.
Ive kept up with some literature and know that relapes when they happen generally do so in the first 3 months. I was encouraged to see that those who loose MMR usually regain it again.

I would strongly prefer to do dose reduction or tfr with medical supervision and hence the need to find oncologists who are positive towards this course of action.

Eva,

My doctor and I have an agreement … if I do anything outside of our treatment plan, I tell her. That includes me telling her if I stop taking my pills (I never have), or anything like that. She says she can’t treat me if she doesn’t know all the facts, and she will treat me non-judgementally. 

What would happen if you just halved your 400mg imatinib pills and told your doctor that’s what you are doing, and you want more regular PCR testing for a while? Would your doctor refuse to treat you any more, or maybe you could just force their hand?

David.

Id have to get my insurance to sign off on the extra tests, which requires a medical report.

He couldn't stop me but it would get expensive (is about 400usd for bcr/abl).

For optimal results I do feel it's important that the doc is 'in it' with the patient and supportive of the plan of action. Last thing i want is a doc who is more concerned than me about a negative outcome.

EvaH, when I reduced my Gleevec dosage I did so by doing each reduction six weeks before my next quarterly test, eliminating the need for monthly testing that most oncs require.

2014 U, U, U, U (12/07 began dose reduction w/each continuing undetectable)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR

Although I did 50mg steps during dosage reduction,  300mg, 200mg, 100mg should suffice for you.

Alternating a whole tablet and a half tablet achieves the 300mg average.

PS: my onc was adamant that I stay on full dosage despite my constant lobbying for dosage reduction ... she only relented when I said I was finally going to reduce my dosage despite her objections.  Even then I ended up with Peripheral Artery Disease in my legs from taking too much Gleevec for too long.  It's debilitating.

How did you do 50mg steps? Were you breaking 100mg in half? So far i didn't see 100mg compunded caplets only capsules which would be tricky to half.

Thanks for all the replies so far, i understand i can do this on my own.

However I'm still looking for recommendations on doctors who will work with me to dose reduce. Anyone has a doc or hospital they've worked with?

(Anywhere except USA/ Canada)

EvaH, I both, split the 100mg pills, and alternated dosage, during my lengthy dosage reduction; i.e. 300mg one day and 200mg the next.  

You mentioned something about withdrawal, tell me more?

EvaH, during dosage reduction and TFR a percentage of CML patients experience withdrawal syndrome.  The pain they experience ranges in intensity, and duration.  Typically joint, muscle, bone, tendon, ligament, nerve pain.  Fortunately, of the percentage beset with withdrawal syndrome, most only experience moderate pain for a relatively short period of time (weeks).  However for a few others, the pain is so unbearable and enduring that they may choose to restart their TKI.  The length of time and the amount of TKI a CML patient has taken likely contributes to the probability of withdrawal syndrome.  When Gleevec was first trialed and then introduced in 2001 many of the early users were put on high doses, 600mg and 800mg, were not unusual, and they were kept on those high dosages for a prolonged period of time (over a decade).  It is upsetting to me to think that CML patients could be unnecessarily kept on a high dosage TKI for that long ... most had been undetectable almost the entire time.  

My own withdrawal syndrome experience wasn't at all typical; it began when I had reduced to under 200mg of Gleevec, and lasted for a year after I began TFR.  My pain centered around a prior fairly severe neck injury impeding/compressing nerve bundles which effect the muscles in my shoulders, upper back, arms, and hands.   The withdrawal problems began in my shoulders and progressed very slowly down my arms, into my elbows, forearms, wrists, and hands and then very slowly progressed back up again.   At times the pain was intense and included joint, muscle, bone, tendon, ligament, nerve pain but then again I had been dealing with pain for decades.  Almost five years after TFR I still occasionally experience intense pain in areas remembered from my withdrawal syndrome; fortunately they disappear in a day, or so.  That in itself is somewhat perplexing to me; how can something hurt that much, and be so sore, one day, and be gone the next.  

Hi Buzz, congratulations for keeping TFR successful, I don't think I had read from anyone in this forum who had achieved it with first-line imatinib, any advice, nutritional, supplements or any other type that you could share in your process? Thank you very much, a greeting.

Jmbnccyn, thanks for the response.  I think it is of utmost importance that CML patients take as little TKI as possible, and begin gradual dosage reduction at the earliest opportunity.  The less TKI we take over the longterm the better off we are likely to be; this especially applies to seniors.  Knowing what I know now, if I had it to do over again; I would have started on a reduced Gleevec dosage (300mg), (the suffering on 400mg wasn't appreciated) and would have began gradual dosage reduction two years earlier probably eliminating at least some of the permeant side-effects I am left with.

I attribute my maintaining TFR so far to my age.

 

JMB I do hope you realise, its too early for you to be considering dose reduction or tfr!

Hemotologists vary on when this can/ should start. Buzz is an advocate for asap, as you can see and he speaks from his own experience where he feels he could have avoided a health condition by stopping/reducing earlier. Bear in mind doctors see many more cases than we as patients do.

In Switzerland i was told 8 years of MMR, at minimum before considering my specialist here would say unless side effects were unbearable, never come off TKIs. UK docs will likely tell a different story.

Buzz: the above remarks are because i know a little of JMCs situation based on his other posts. Not intended to question the validity of your advocacy. :)

EvaH, the Stop Studies only required two years of contiguous undetectable to participate.  

In addition, although all CML patients won't reach undetectable, or be able to attempt TFR, an extremely large majority will be able to reduce their dosage to a very low level for the longterm ... well over 90%.  

Hi

I tried TFR a few years ago. In autumn 2017 I halved my dose of imatinib to 200mg, I remained in MMR and in autumn 2018 I stopped taking pills. In April last year, 17 months in to TFR, my BCR-ABL went above 0.1% for the first time. I restarted on 400mg, and got back to below 0.01% in 5 months. I am now getting 0.000% results in BCR-ABL, and in discussion with my consultant on reducing to 200mg again. Although my side effects on 400mg are not as bad as first time round, I would like to try 200mg. I doubt if I will try TFR again; I think I'll be comfortable on 200mg. My consultant is going to discuss my case with other experts at a meeting chaired by Prof Copeland from Glasgow in early July; I will advise the forum of the outcome.

The reduction from 400mg to 200mg had a bigger impact on side effects than stopping from 200mg. I talked about this at the 2018 CMLSG patient day in Birmingham; that video is here  if you want to see what happened.

The video I would recommend you definitely should watch (and probably get your doctor to watch) is this. At the 2019 patient day Prof Clarke talked about "Reducing or stopping treatment - who and when?"

I hope this is useful

 

Good info. I certainly feel ready to try dose reduction and have felt this for a while. Despite what docs have said to dissuade me :)

Btw, The other forum user is 6 months post Dx. Im not sure he is undectable yet but a clear case of too early.

Hi Eva, the truth is that although I want things to go as well as possible in terms of results, the possibility of reducing doses and much less tfr is not only not in my mind now that I have a suboptimal response to imatinib, but that I would not be in my mind either, nor in the hypothetical case that my answer was good and lasting, it would give me too much anxiety and if things go well, I think better not to touch them, so I am fully aware that I will probably never reduce doses, let alone tfr , My comment was more focused on that buzz, who has done so well in his response to imatinib, could give us some advice at the diet level, supplements etc, all information is valuable and welcome, even so, thanks for your answer, a greeting .

EvaH, just to clarify, I believe in beginning gradual dosage reduction as early as possible.  In your case that would have been three years ago, after you achieved a year of undetectable status.  An appropriate TFR attempt would be after five years on a TKI with at least two years of contiguous undetectable status.  From the Stop Studies, CML patients with at least five years of TKI usage, had better TFR success rates.  TFR success rates also improved with age.  

Worst case, in all likelihood, you end up on a very low dosage of Imatinib; i.e. Imatinib 50mg..

EvaH, if and when you do gradual dosage reduction, followed by a TFR attempt, If you fail TFR, it's worth arguing to restart on a low dosage.  When CML is at a very low level, such as after failing TFR, it only requires a low dosage of a TKI to suppress it.   Hope to be adding to the following cases.  https://communityview.lls.org/users/buzzm1  The success rate is 100%.

Wishing you the best,
Buzz

Thanks buzz, ill be following the community and hopefully adding to the success stories

Eva:

I would echo much of what Buzz has said.  I had horrible side effects from my initial 2016 starting dose of 300 MB 2x/day Tasigna, including 40 - 50 squamous cell skin cancers in a 4 month period, terribly swollen salivary glands, mouth sores, dry mouth, fatigue, intermittent GI problems, headaches, tinnitus, muscle cramps, irregular heartbeat, etc.  I was miserable and so I started lobbying my onc for dose reduction as soon as I hit MMR, which occurred in just under 90 days.  At 6 months, he finally relented and allowed me to reduce to 450 mg per day, but insisted on testing every 6 weeks. Over the next 6 months, we did 2 more dose reductions, first to 300 mg/day then to 150 mg per day.  Most of the side effects were gone by the time we got to 300 mg per day.  During this period, my PCR also dropped from .1% to undetectable. Unfortunately, the irregular heartbeat continued and I started to develop peripheral neuropathy symptoms.  I asked my onc to approve a switch to 20 mg/day Sprycel, but he wouldn't permit it, so last summer I attempted TFR, but with the explicit understanding that if I failed, I could restart at 150 mg and not full dose.  My onc agreed but we set the failure bar as any PCR worse that .01% rather than .1%.  In 75 days, I hit .02% and restarted 150 mg/day Tasigna. 

About 3 months later, I finally convinced my onc to allow me to try 20 mg Sprycel and I have now been on that for nearly 6 months and just reached undetectable again last week.  I have little to no side effects so I feel that this is more tolerable for now than Tasigna.

I believe with all my heart that dose reduction should be started once a patient achieves and maintains MMR for 2 consecutive 3 month tests.  The goal should be the lowest possible dose while still maintaining MMR.  In your case, you have far surpassed MMR and you need to lobby your onc hard for dose reduction.  If unsuccessful, find an onc who will allow this.  The money saved by lower dose more than pays for the extra testing.  Sign a liability waiver if you have to, but you are long overdue for dose reduction and then possible TFR.

Good luck

Thanks Jax

I've sent a request and some literature to my specialist. He looks to be in his 70s so i doubt he will change his mind.

This brings me back to my original appeal for names and locations of specialists in Europe who are positive about dose reduction. Because later in the year i may have the freedom to pick up and go.

Hi Eva, as you note in the first post on this thread I think you would get a favourable view on this from most of the UK CML Experts. If you click on the "Patient Info" tab above and then select "Specialist Centres" you will see where the main centres are located in UK. My consultant in Chester is part of a regional CML group which Prof Clarke started in Liverpool; Prof Clarke was the lead researcher on the Destiny dose reduction/TFR trial, and gave the paper on the link on my 9 June post above.   My previous consultant in Durham was a member of a similar group in North East England with Prof O'Brien in Newcastle.

I failed TFR last year after 17 months off the pills, having maintained MMR on 200mg Imatinib for a year before that. I went back onto 400 mg and am back at 0.000%, and asking to return to 200mg. My consultant is discussing this with some colleagues in a few weeks time, and I am fairly confident he will agree.  

Thanks for your story and the contacts!

I asked my doc about dose reduction and he sent me back stopping treatment criteria from the National Cancer Centre in USA (I fit 100% of the criteria) but I'm not read to stop yet, I am ready to dose reduce. 

Eva you're absolutely taking the best approach in my view. When I reduced to 200mg I lost around 75% of the side effect impact. Prof Clarke talked about how people got on at half dose as being a good indicator of likely TFR success .Destiny showed that a higher % of people achieved TFR after a year on half dose than people who went "cold turkey". Good luck