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Treatment break and PCR increase

Hi all.

Just would like some opinions if possible. I have been on before about the issues I have regarding side effects since diagnosis.

I was diagnosed June 2013 at 33. Superfit. I am a firefighter who has still struggled to resume normal duties.

After pain around body, mainly neck, arm and but also other joints my consultant decided to give Nilotinib a break. The break started end of November when my PCR was 0.00... Fast forward to 26th February and my consultants screen looked like this...

December... PCR 0.00
January... PCR 0.05 - BCR/ABL: 58
February... PCR 1.5 - BCR/ABL: 768

Basically I saw a new consultant at my centre for excellence who seemed to be of the opinion this was increasing 20 fold and my next PCR taken the day of my visit could be considerably higher. He mentioned that messing with treatment can very much increase your chances of the disease progressing and becoming acute. He said looking at how quick the result was climbing if it continued without treatment or if there was a treatment problem, this would probably mean a 2 year survival.

I was originally taken off Nilotinib, I would say I felt 50% better, my main benefit was feeling so much more energetic and the clarity of mind. I have since been referred to see a Neurologist, his initial opinion was the pain I was experiencing in my arm and neck could be nerve damage from the TKI's. Nerve conduction happening soon.

I am quite confused about all this. I just wanted to hear if my latest PCR results look alarming to other CML'ers. My wife was in tears when she listened to the consultant and I have tried to reassure her.

The confusion surrounding TKI's seem to get compounded on each medical opinion I get from various departments.

Anyway I have restarted Nilotinib at 150mg ONCE a day. Even though I would of quite happily went to what ever it takes to get my PCR down and mentioned this.

Is over 2 month too long off Treatment? Could this have very bad consequence at a later stage?

I did get a nice kiss off my 15 month old when I came out of the appointment, maybe because I had just given him a cookie however! So that was the days high point!

Take care all! Thanks again for all your help in advance!

John

Hi John, I hope you're doing OK.

I guess your consultant sounds concerned at the rate of increase, rather than the raw figure.

Looking back on some of my results, I went from 12.6% to 76% in the space of 15 days off medication in the earlier days.I remember my consultant being surprised at the rate of change, but of course as soon as I went back on TKIs (a different one) things moved down again.

The 2-year survival sounds shocking, but that sounds like a 'treatment-free' prognosis which is quite different to anything else.

If it's any help, it took me about 18 months from diagnosis to get to around 1.5% so although I know it's not ideal it doesn't sound like a shockingly high figure but it's the rate of increase that you need to be aware of.

I'm sure someone will be along shortly with a better understanding of the implications of being off TKIs for a while, but as I understand from the stop-TKI trials, those that don't manage to keep their PCR low when off medication do just fine when the TKI is reintroduced.

This thread, from just today, shows that you can take a break - go up in a not great way - and get back down again.

http://www.cmlsupport.org.uk/node/8886

David.

Hi John,

I think the rate of increase may not be surprising given you were without treatment- but the actual results - 0.05 and 1.5 are not that concerning providing you have resumed treatment. I don't think you should be too fearful of taking a break from therapy- The concern is for the long term regular lack of adherence- i.e regularly missing a few doses each month - rather than you kind of managed treatment cessation. I am sure you will see a quick response with a reduction in your Bcr-Abl % back down to the molecular levels you saw before. Most people who are able to maintain their molecular responses without treatment (Treatment Free Remission) have had very stable low level MRs on therapy for at least 3 years (the longer the better) before attempting to stop. Even so, most do see a return of higher percentages of Bcr/Abl some have molecular relapse quite quickly (like you) and some take up to 9 months before having to resume treatment- but to my knowledge, all those on the stopping trials (STIM) who saw a molecular relapse and then resumed therapy regained their previous responses eventually and none saw disease progression.

I am surprised that your consultant has not suggested that you try another TKI- such as dasatinib or bosutinib- because your side effects had improved (by 50%) during your treatment break.

If I were in your shoes I would ask to discuss this option as a possible answer to your pain.

I hope you are reassured by both David's and my own response to your post. If it helps, I know at least one other member of this forum who is in the same age group and is suffering the same level and kinds of pain as you are- (he also is treated with nilotinib).

Best... Sandy

Hi Sandy and David.

Many thanks for taking the time go respond with your thoughts on this. I have showed my wife your posts and it has made her feel somewhat better.

I will keep you informed of my results in the next few month and hopefully I will report a drop as TKI's do their work.

Regarding another TKI, I was told I would only have access to Dasatanib and it tends to be worse than Nilotinib for side effects. His advice was to try and tolerate Nilotinib, and he doubted that the CML or the treatment was the factor and suggested something else may be the culprit. However when I was asked to give my account of the following 18 month he then said it could be treatment but its unusual... This is what is making me feel a bit confused and in a sense anxious to what is going on. I have no one else to compare with, I had over 2 month off treatment and half of my symptoms stayed. Half went, rashes cleared, brain fog cleared, energy levels went back to feeling like I did before diagnosis. The most bizzare I have had return is red, itchy, burning eyes like hay fever after shower or bath (Not the end of the world by any stretch, but odd).

I think the thing that keeps me up is my pain and creaking and crunching joints. I am desperate to get a pain free week in, and build upon it. For past 18 month, I have had possibly 3 weeks pain free. I have been on light duties as a Firefighter since June 2013 and I am desperate to get back to what I have worked so hard for, love doing, and also for the financial stability for my family. I am having a medical next week and don't know where to begin!

Sorry to sound like a pain to everyone, its just I feel quite lost and with my healthcare saying different things and lack of answers. Haematology, rheumatology, nuerology and GPs.

Thanks all. Take care.

When I read your posts since several days, I understood that I am not alone to suffer of these bizarre pains on nilotinib. I suffered from neck pains (burning senation, electric discharges), headaches (like being stabbed) before my diagnosis in april of 2014,I couldn't move any more. Then pains disappeared thanks to Hydrea and nilotinib (in the first time) during several months, but they came back since October 2014, every day all the time, no remission. Like you,I am young and father of two young children, I have a struggle to work in good conditions. I can't get used with this situation (joints pains every where too) and like you I saw different specialists : Rhumato, Neuro, even my hemato told me that tki and illness couldn't give these kind of pains. All analysis seem to be normal, except may be cml because in my last appointement the decrease was less than before. My onc is formal : At these levels of desease, cml can't give me these pains. Ok, but why theses sufferings are the same before my diagnosis? No one can answer me, I suggest like you that Nilotinib may be one of the reason and I will beg for a change of tki to Dasatinib. But oncologists are overcautious with it because of pleural effusion, and also because I am young and there is only few options. I am ready to "take the risk" as I can't live like this anymore. I hope that new tki will be available in the future to have more choice and more chance to avoid all these problems some of us have to overcome. Sorry for my English but I have got a big excuse : I am french ;).

Hi John,
It is hard to find a credible reason for your side effects other than they were/are triggered by TKI therapy- i.e nilotinib- or at least some of them are directly caused by NI and others may be from a general downstream effect of the drug. Even though you have a very good clinical response the level of pain you are enduring can only be described as a grade 4 side effect and in my opinion you should be offered the chance to try another TKI to see if the effects are any easier. Dasatinib is the first option as it is available through the CDF but only after you have tried imatinib and/or nilotinib and proven to be either resistant OR intolerant.

To my knowledge the side effects of each TKI do not necessarily cross over. Dasatinib is known to cause pleural effusion (fluid on the lungs) which is reversible, but this is not an issue for the majority and many people treated with dasatinib find it a suitable alternative to imatinib or nilotinib.

Should you not be able to tolerate dasatinib, you would be eligible for treatment with bosutinib through the CDF (unless you move to Scotland where it has recently been approved for routine NHS use).

You may need to try and persuade your doctor to help you at least try to conquer the constant pain by changing to dasatinib. As you did not have this before being treated with a TKI then it seems a little short sighted to deny that this could be the cause. Maybe a second opinion would be something to consider?

Sandy

Hi Frenchguy/Sandy

Thanks for getting in touch and sorry to hear you too are experiencing pain. First of all, you are more than welcome to send me an email if you need to chat ever. I am sure Sandy can pass this on for you. Secondly your English is very good so don't apologise, it's way better than my French. Have you been given anything for the pain? I have been given Pregabalin and have found that has helped. Hopefully you will get that change and it has the result you are looking for. Hang on in there!

It sounds like you have seen the same sort of medical referral pattern as me, in the sense you have seen a rheumatologist and then get sent to a nuerologist. I am just hoping this is not a nerve damage thing and the test is clear. What tests did your Neurologist do? Have you been given a treatment break from Nilotinib and if so how was that?

Sandy, thanks again for your reaponse. I really appreciate your compassion and advice. I really do hope this is just a temporary thing, however the fact I was off Nilotinib for over 2 month and only seen some improvement really worries me. I keep mulling things over and over. My team said the treatment should of completely left me after 2 month.

Regarding a second opinion, I am with Newcastle's centre for excellence and see the top guy there. Dasatanib has been mentioned, however, two consultants seem to be swaying away from the treatment causing me issues as I still experienced problems whilst on the break from Nilotinib, although some issues certainly resolved. The main issue my back, neck and arm were only somewhat better. I have asked rheumatologists, heamatologists, neurologists, GPs and physios if this could be neck problem but have been told that an MRI only showed very mild disc bulge and this categorically can't be causing me the issues, all of them having read the report.

I even asked if the CML could of created or even be creating an issue with my body, but I have been told that's not their opinion. However if our bodies are battling this chaotic molecular problem, would it be out of the question that some people, maybe a minority, were affected differently. I keep getting told from haematology that we maybe can't lay the blame at the foot of the door of CML or TKI's... I am not, I am just of the opinion if is not the CML, or the TKI's then I need to find where the blame lies and treat or manage it... However being super fit, never having a medical problem, then presenting with issues prior to diagnosis and then this gradual slide seems to me too coincidental!

Anyway sorry to again to everyone for whinging on. Just frustrated at seeing my notes shifted from trolley, to drawer but not being able to plan anything, more kids, moving home, employment.

Take care all.

John