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Long term effects of tki's


Hi All,
Having been on Glivec then imatinib(Sandoz brand ) for just over 17 years a subject that interests me is do the side effects of a tki get worse as one progressses with (often lifelong ) treatment or do some disappear as one becomes use to them?
I cannot find a lot in the medical literature on this subject.
The side effects that have affected me are :
Occular issues-periorbital odema (swollen tissues around eyes),blepharitis(swollen eyelids) ,conjunctivitis,eye bleeds/haemorraging.Most of these are manageble and some self limiting.
Musculo-skeletal issues:muscular cramps especially at night,myositis with raised creatine kinase bloods (inflammation of the muscles).joint pain and non diabetic peripheral neuropathy (nerve deterioration in legs and feet)
Diarrhea/ faecal looseness and gastro intestinal discomfort/diverticular disease,ibs/ibd.??
Heart issues-atrial fibrilation
Nausea/headaches and vomiting after taking the pill (solution is to take the pill with a substantial meal and drink two glasses of water )

Immune or auto immune related issues are always in the back of ones mind as it is thought that tkis may affect the strength of the immune system.
Auto immune issues can be rashes including dermatitis of the scalp,muscular inflammation and intestinal weakness as examples-the immune system goes into overdrive and attacks normal cells.

In addition one hast be aware of drug/drug interactions between imatinib and other medications/treatments :mine is balancing out a blood thinner with imatinib as one potentiates the other and it can lead to bleeding internally for example.But I have been told that a thinner will safeguard against having a stroke-so it is a balancing act which is not uncommon in medicine.I would never take ciprofloxacin antibiotic again as previously it gave me horrible and disabling muscle and tendon/joint issues-unless I had to be treated for anthrax

Comorbitities-an old question is does having CML and being treated for it make one more prone to other cancers such as prostate,pancreatic, breast .ovarian ,cervical,bowel etc etc some of which are still real killers.

I asked my specialist about these matters of long term effects and he said occular and musculo skeletal are directly related to imatinib .Diarrhea is a common side effect as well but whether it leads to diverticular disease is open to question -diverticulosis is very common anyway in the general population in old age and for the over 80s for example 75 % of this age cohort suffer from diverticular issues as the intestines etc lose their strength and functionality.He said many cancer drugs and chemotherapies had this specific side effect of diarrhea and sometimes quite severe.

Atrial fibrilation is a very common heart complaint in the general population and many out there are not aware that they have this flutter until it leads to complications like a stroke.Whether imatinib is hard on the heart is not really evidenced I believe so it is difficult to blame the drug imatinib.

Some statins like simvastain have side effects on nerve functionality in the feet and inflammation in the muscles so we cannot always put the blame on imatinib.! Pravastatin apparantly sits quite well with imatinib compared to the alternatives.

I asked if it was possible to measure the strength of ones immune system-he said it was difficult except if one experienced continual infections
then this would indicate a weakened immune system.

In respect of choosing an alternative tki I was advised that if one has a history of any pulmonary disease then the risk of pleural effusions with dasatinib was enhanced and far greater than the normal level of 1 in 5 .Professor Jane Apperley from Hammersmith said that nilotinib was hard on the heart so if one has any form of heart issue be very cagey about going that route.
Treatment free remission is not an option for me as we tried it 4 years ago whilst I was having radiation implants of iodine -125 for early stage prostate cancer (now totally zapped) and my loss of mmr was rapid and alarming and it took a year to get it back;so I am on a tki for life it seems.

The majority of us on a tki will find that another condition rather than cml will get us -in the meantime the challenge is to manage the side effects which your haematologist will tell you are still relatively mild compared to some chemotherapies for example for aml and other cancers and they in some instances also only prolong life for a short time span.

Does anyone who is a long termer have any thoughts and experiences about long term side effects of the tki that is your current treatment ??



John my experience is very similar to yours in terms of duration (17 years now) and medication (imatinib).

On 400mg after initial fairly intense bone pain settled down I certainly had oedema in face and lower limbs, occasional gastric upsets, regular flatulence, quite severe cramp during and after exercise and eye bleeds once or twice a year. When I reduced to 200mg all of these were significantly improved, and when, a year later, I tried TFR, the improvement at that stage was less marked than the change from 400mg to 200mg. My TFR failed after 17 months and I was concerned that I would go back on to full blown side effects when I went back to 400mg. I was surprised that they were not much worse than I had experienced on 200mg, and when I returned to 200mg after 12 months at MMR all became quite tolerable. That coincided with having an arthritic hip replaced with a shiny new titanium one, which has enabled more exercise, weight loss and energy.

I'd rather not be taking any TKI but I'm not tempted to try TFR again.

Hi John,

I’ve been a member of cml “club “ going on for 10 years, and have mentioned before for the first six months was on imatinib, after being told it had failed, I was put on 800mg Nilotinib which I always remember my consultant saying, “I hope you have a strong heart “ . Years later I’m still on the same dosage, and tki, but have had bladder surgery, put on statins, told I have type 2 diabetes and now there carrying out liver damage checks as my Cml blood checks keep raising concerns about my liver, no doubt tki medication is a wonderful, life saving medication, but like any drug it makes you wonder, can your body cope with powerful drugs without damaging organs in the process.

Take care John,


The higher the TKI dosage and the longer you are on it, the higher the probability that you will suffer from the side -effects of the TKI, possibly causing permanent damage.


That has always been my thinking. so I cannot understand why my doctor is so reluctant to even engage in a conversation about lowering my Sprycel dose below 50 mg. Shouldn't everyone be on the lowest possible dose that works for them?

That has always been my thinking. so I cannot understand why my doctor is so reluctant to even engage in a conversation about lowering my Sprycel dose below 50 mg. Shouldn't everyone be on the lowest possible dose that works for them?

That has always been my thinking. so I cannot understand why my doctor is so reluctant to even engage in a conversation about lowering my Sprycel dose below 50 mg. Shouldn't everyone be on the lowest possible dose that works for them?

That has always been my thinking. so I cannot understand why my doctor is so reluctant to even engage in a conversation about lowering my Sprycel dose below 50 mg. Shouldn't everyone be on the lowest possible dose that works for them?

(no idea why that posted four times - so sorry)

Thanks Alistair Buzz and all,
I find your case Alistair interesting and relevant that you after under performing for TFR found that 200 mg allows you to tick over and maintain your MMR.
Going back to the original trials for Glivec Phase One led by Brian Druker on the west coast of USA in 1998 (source Magic Cancer Bullet -Daniel Vassela with Robert Slater published 2003) they found that lowish doses of say 85 mg were ineffective but that doses like 300 mg led to rapid reduction of white blood counts .I suspect that 400 mg was chosen as the essential standard dose so as to make sure that a largest cohort of patients possible could achieve MMR within a reasonable time frame.Novartis eventually in their product literature stated that 600 mg and 800mg of Glivec could be administered if required.
The body of opinion on here from experience suggests that some long termers a reduced dose of say 200 or 300 mg of imatinib might allow us to retain MMR but at the same time minimise side effects.The same has been put forward for Dasatinib re the possibility to reduce the dose from 50 to day 20mg per day.
I suspect that many specialists are reluctant to reduce doses because they have little experience of long term use of imatinib as CML is quite a rare condition-perhaps about 800 new patients in UK diagnosed each year.
In my case a recent meeting with my consultant suggested that imatinib might well have caused my long term faecal looseness but as to whether we can attribute the drug as cause of diverticular issues we cannot be sure.My heamatologist has asked my GP to organise a FITT test to check for microscopic traces of blood in poo and then we go from there according to the result.In August 2023 I had a colonography -a virtual colonoscopy involving a specialised CT scan of the intestines etc and nothing substanctial showed up
On this Forum Alistair and myself seem to to be some of the veterans on Glivec/imatinib.Sandy Craine would have been one of the longest users of Glivec/imatinib having been involved in those US trials back in the late 1990's and perhaps the first user in the UK after the drug was licensed by FDA in US and NICE in England/Wales-she regretfully is no longer with us.

SageH, unfortunately not all doctors believe in dosage reduction. If you think your dosage should be reduced and your doctor refuses to address the issue, either find another doctor or begin to reduce your dosage on your own. Ultimately the dosage you take is your responsibility.

In my own case I took Gleevec 400mg for almost five years. After three years of Gleevec 400mg I began lobbying my doctor to reduce my dosage to which she constantly refused. After almost five years I told her I was going to reduce my dosage with, or without, her, and began a two year gradual dosage reduction, and finally, TFR..

I ended up with Peripheral Artery Disease which greatly reduced the circulation in my legs, which I attribute directly to the prolonged unnecessary Gleevec 400mg dosage. It has been almost ten years of pain and suffering and struggling to maintain which is why I encourage CML patients to begin to reduce their dosage to as low as possible as soon as it is feasibly possible.


Hi Buzz
Your peripheral arterial issues are bit like my non diabetic peripheral neuropathy-thinking through some of my additional side effects many of these could be autoimmune issues.Rashes, scalp irritation and lesions ,myositis and muscle inflammation,inflammatory bowel disease ,neuropathic decline are all auto immune effects-like you perhaps I suspect that full dosage tkis eventually lead to a compromised immune system.However auto immune clinics and experts are few and far between and tend to be rheumatologists or endocrinologists for instance.A few chest physicians will understand pulmonary sarcoid conditions that are very good examples of auto immune disorders.

Hi, John, it's Kat and I'm here too! At 15 years in, not the longest vet, but I certainly feel like a somewhat battered 73 year old vet. My Gleevec experience was very much like yours. I was allowed a couple of early breaks from treatment, then returned at 200 or 300 mg at which level all my side effects were much improved. But back at that time, the oncs would not let you stay there, so back I'd go to misery at 400 mg. I bore up for two years and then switched to dasatinib. Immediate and substantial improvement in side effects! Is it fear of pleural effusion that has kept you from trying dasatinib? I did get that - won't recount the story - but I live without any symptoms from a minimal residual amount of fluid on 20 mg of dasatinib.

To address your original question to us old-timers, yes, as the TKI years have rolled by and the regular aging effects have kicked in, I have noticed the side effects getting worse. My face has fallen at an alarming rate and the eye bags and fat lids and puffy overhang of my eyes make me quite unhappy. I knew dasatinib shared some off-target effects with Gleevec, but in the beginning years, the difference between them was amazing. It has only been in the last 5- years that things have gone sideways. But as you said, the stuff that happens with plain old age is very hard to untangle from TKI side effects. I'll probably not get to TFR. I am, however, interested in asciminib as a possibility for getting out from under the eye bags, as it has a completely different site that it targets. Have you thought about it? I'd love to hear what former dasatinib and imatinib people have experienced by making the switch to asciminib.

I was diagnosed back in 2003 (at the age of 39) before NICE had approved funding of imatinib but managed to get it through my BUPA health insurance. I was so grateful. Like most of the other replies i had eye bleeds, loose bowels and muscle cramps but all were manageable. I was moved on to Nilotinib a few years later to get a lower response and had very few side effects at all. (The opposite problem to imatinib was the constipation but again not severe). BCR is below .01 and dose has been reduced to once a day dose of 400 but i am not expecting to ever be off the drug. I am not aware of any health problems that have been caused by the long term use of TKIs. I had 2 breast cancer diagnoses before the CML which are probably related to a gene mutation and has not relation to the CML.

I was diagnosed in 2000 at age 12. I have been on imatinib (2002 - 2007) and now dasatinib (since 2007-). Had a few treatment interruptions for IVF/pregnancy and a TFR attempt. Unfortunately, the disease came back after any interruption or dose reduction (I was resistant to imatinib due to some mutation, and I think if you got any resistance to a TKI, you can never go treatment-free or even reduce your dose ever). I do have higher BP levels (in the 140s and also have a strong family history), and I am 36 now. I have a permanent puffy under-eye area, a puffy face, and nausea if I do not have food with my medication. And I also have skin pigmentation hair thinning issues, but they are minor inconveniences. Thankfully, no other long-term serious side effects so far. Hoping to stay that way for a long time.