You are here

How to manage side effects of anti-CML tyroisne kinase inhibitors?

Categories:

Dear CML Forum,

I am a new member and just now created my account.

My mother who is 75 years old, got diagnosed for CML in November 2020 in India where she lives and was commenced on Imatinib 400mg daily as her treatment.She has a background of hypothyroidism( takes 100mcg Eltroxin daily), chronic depression( takes Paroxetine 12.5mg) and difficulties with night time sleep( takes Zolpiderm 5mg daily).

Initially she responded well with her blood counts normalising within few weeks but by the 6 month, she developed gastrointestinal symptoms of frequent loose stools, nausea and crampy abdominal pain.These were initially managed with SOS use of Loperamide, Antispasmodics( Buscopan) or Tramadol if need be and taking daily Probiotics( Bifidobacterium), but gradually these were not helping too.

Her treating Haemato-Oncologist, then checked her BCR-ABL gene load which was still high( only 18% reduction) and ruled out any new mutations.Then treatment changed to Nilotinib( Tasigna) on the basis of intolerance to Imatinib and lack of expected molecular response.Unfortunately my mother couldnt tolerate Nilotinib within a week of starting it due to lot of body/back ache, tiredness, breathlessness and some abdominal pain with loose stools.

After 2 weeks of starting Nilotinib and developing above concerns, plan was made to retry Imatinib but at a lower dose of 300mg daily, see the response for a month or so and if no success then consider changing to a third TKI-Dasatinib.

The latest and current dilemma is that my mother had the same Imatinib side effects even on reducing dose to 300mg( mostly GI symptoms) and so after one week, she was changed to Dasatinib last week at a dose of 50mg daily.Unfortunately within 2 days of Dasatinib, she is experiencing lot of generalised body ache, weakness, headache and feels very miserable.Taking good doses of Paracetamol helps only slightly.

I feel as trapped in a big dilemma for how to manage the side effects in a satisfactory manner so as to allow compliance with treatment.

My questions are-

1 How much can we lower the doses for Imatinib( ? 200mg or less) or Dasatinib( ?25mg or less) or Nilotinib so as to minimise all above side effects and then be able to continue to take one of the medicines as long term?

2 For her elderly age and already being 75yrs old, is it necesary to keep a treatment target of deep molecular remission as this will warrant full doses of the respective medications and will not be easy?

3 Are there any better strategies to manage the side effects besides using Loperamide, anti-spasmodics/pain killers?

4 Is it common to see such side effects with all the 3 medicines mentioned or I need to consider some non CML reason( she possibly has some IBS), ? contribution from mental health issues?

What will happen if no TKI treatment is taken at all?Will she worsen to Accelerated phase of CML much earlier?

Will really appreciate some bright ideas and support please?Dr ST.

Gastro issues are common on imatanib. How bad was it? Most of us manage some level of side effects and it cam get better with time.

She seems to be switching meds very often so she cant have been on any one type for very long. Go back to imatanib and stay on it for 6 months and live with the GI issues!

Also you mentioned she is based in india, is she taking Veenat? If not which imatanib is she on? Might be worth switching to Sandoz or Teva generic.

Given the history you describe, I'd say its a fair chance that polypharmacy is an issue. Being given regular sleeping medication is a bit of a red flag that she is being stuffed full of drugs so that she doesnt make problems for the people in her life. If you read the mechanism of action of zolpiderm, no one should be on it permanently. Id also question a diagnosis of chronic depression that is managed solely by medication without any thought to lifestyle factors and/or counselling or meditation.

To answer your questions more directly, MMR is not needed to live a normal life.
At 75 she can have 10-20 years ahead of her so dont focus too much on her age as reason not to treat.

Stop focusing on trying to eliminate all side effects from tki. It aint going to happen, and things can settle fown after time. But not if shes getting meds switched more often than she goes for walks in the park.

What TKI side effects can she live with? Were the GI ones so bad? I assuming she doesn't need to work, commute, look after family, earn a living like many of us do so the question is how much interference is happening in her daily life?

Have you ask her what side effects she can and cant live with?
(Understanding that she will have some, at least in the beginning)

I have to endorse @Evah's comments unfortunately TKIs come with side effects.  I am someone who struggled with Imatinib for a long time and still do occasionally (nearly 10 years later) not helped by the Uk medic view at that time that such side effects were rare and only lasted 4 weeks, unfortunaltely for me at that time there were medical reasons why I could not take the only other first line TKI Nilotinib so I just had to get on with it and work etc.  I went home to care for my mother and in my home country the medics moved me on to 300 Imatinib taken in 100 after a meal three times a day and it helped quite a bit.  I was told on return to UK that I had to go back on to the once a day 400 but stuck to my guns re the 300 regime and achieved MMR in reasonable time which I sustaiined until a recent illness compelled me to come off TKIs for a while.  The Diarrohea can be controlled, the nausea usually wears off after half an hour and can be avoided by taking straight after food with large glass of water but when you have a holiday from treatment you realise how much Imatinib messes up your digestion, on the other hand for me it has little effect on energy and has enabled me not only to live CML free through my sixties but also to carry on working walking cycling riding etc.  It is worth looking at the different versions of Imatinib as Eva suggests I found some of the generics hard work and ended up back on Gleevec when the price came down  

1) First she must get to MMR, which is 0.1% IS.  After that, she is much, much safer and it isn't so very imperative to get any lower, factoring in the possibility of intolerable side effects.  The target for this is a year, BUT MANY people don't make that target and take longer and they are doing great.

2) Answered above.

3)  For imatinib, she MUST have some food in her stomach.  Some people need to wait an hour, but others need to take it while still full.  Water is not the answer.  She must give it some time, be patient and have faith the medicine will work.  However, having said that, these early days are very, very stressful and lonely and miserable.  I am still appalled that after all this time people are still not getting the emotional support from their oncologists that they deserve in the very early part of this journey. The oncs are just so happy that this is one cancer they can treat effectively, they forget how truly awful people can feel physically and just how scared they are about the future.

4) You should have been given a lot more information regarding side effects.  But, you can find all this out yourself.  Point is, they all have side effects because they are imprecise in their targets and have some off-target spillovers, so your normal body parts and systems get affected.  Most people adjust, their bodies adjust, whatever.  It gets better.  Takes a lot of time.  Some people don't get better and find they can't tolerate the side effects.  But we have imatinib, dasatinib, nilotinib, bosutinib, and even ponatinib.  Somewhere in there, people usually find a fit they can live with.  Plus, reducing the dose helps tremendously in most cases.  You can't reduce, however, until you've given it some time for there to be CML improvement.  If the trend is downward, she's getting close to or has reached 0.1%, and she's still miserable, her dose can usually be adjusted, especially if she's on dasatinib.

For your last question, you know the answer.  If she can find a TKI she can tolerate, she probably will die of something other than CML.  If she is not treated, she will die of CML.

 

Dear EvaH,

Many thanks for your reply and suggestions.

When on Imatinib she was taking Gleevec as the generic medicine and fortunately did well from Nov 20 till May 21 with no major concerns.

I will agree that the long term use of anti-depressants and sleep medications has not been a good thing. She has received  Psychotherapy for these issues even before the CML diagnosis and specifically after the diagnosis but it has not been sustained to get a good benefit from it.I will be trying this out again so that the polypharmacy can be reduced.She does Meditation but may not have the motivation often to sustain it.

Unfortunately as of now, she finds most side effects difficult to cope with ( GI symptoms from Imatinib, generalised body ache, breathlessness from Dasatinib and Nilotinib etc) but it is obvious that none of the TKI's will be free of side effects.I am encouraging her to think and decide for herself what she can bear/cope with and then comply with the medication.

I see that there are some other TKI's like Bosutinib, Ponatinib but i dont think that frequent switching within less than a year of diagnosis is a good strategy and will be focussing on finding strategies to stay on one e.g Imatinib or Dasatinib and manage the side effects or even live with them.

Hopefully with more time, her mind and body will adjust to the treatment and side effects.

Both as a doctor and her son, I will not focus on her age as I know that chronic phase of CML doesnt reduce your life span.

I do think about Quality of life at this age and the misery of bearing the medication side effects but you have given me very good and meaningful answers to build upon- both for myself and her. Kind regards and best wishes for your good health.

You are quite right to focus on achieving MMR while maintaining the best quality of life your mother can manage while taking TKIs other people will tell you their experience some will be quite didactic about what does and does not work but every persons experience is different e'g' one of the above contributors says drinking a large glass of water with imatinib (after food) does not help but I find it does, probably we are both right as we are individuals.  In my home country they suggest that you keep a diary of side effect symptoms and keep making small changes until you discover the best way you as an individual can tolerate the TKI .  this also has the advantage of making you feel as though you and not the drug are in control.  People achieve MMR at different rates so long as the trajectory continues downward don't panic.  I think you are right to take age into consideration too.  I know if I had been diagnosed in my thirties or forties my attitude would have been very different but being diagnosed in my sixties in a family where all my female relations succumbed to Alzheimer's in their late sixties /early seventies made me determined  to keep the side effects to a minimum in what might be my last few years of full faculties so I was prepared to go a little slower to MMR in order to live a better quality of life at the time.  Luckily I am still compos mentis but I am glad to have had  some more good years without major side effects.  Talk to your Mum about how she would like to manage while achieving MMR she will find her way with your help.  Best Wishes.