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Poor response to TKI'S ?

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Hi everyone,

I'm looking for a bit of advice at the 11 month mark.  I was diagnosed
just after my 68th birthday last September (2021) when very ill, with
dangerously high blood figures and a much enlarged spleen.  I started on
Imatinib 400mg, and the 3 month BCR-ABL was 27%.  I was checked for
mutations and MPN, both negative.  The 6 month BCR-ABL was 41%, with
platelets increasing in the routine bloods too.

After a month's delay (due to pharmacy error!), I was switched to
Nilotinib 800mg.  This has had multiple side effects, but the routine
blood results are now good.  The next BCR-ABL was taken at 10 months,
and was 29%.

The consultant is in a bit of a flap -- talking about changing to a
third TKI or possibly a bone marrow transplant!  A repeat BCR-ABL has
been taken this week; she says if it's not down to 10% this time I will
have to change treatment.

Has anyone else been in a similar situation?  Where did you go from here?

Feeling a bit overwhelmed at the moment...

Imatinib and Nilotinib work in a similar fashion in that they bind to the ATP site in bcr-abl responsible for bcr-abl tyrosine kinase and cell division. Once this ATP site is bound up by imatinib, it fails to create tyrosine kinase and ultimately dies (fails to divide). Nilotinib binds a bit tighter to this ATP site and tends to be more effective than imatinib in combating CML. I think of nilotinib as working faster than imatinib and outpacing CML better than imatinib. For many patients, imatinib is sufficient - and in fact is a life saver and transformed a fatal disease into a manageable one albeit with side effects.

Usually when a patient does not respond well to imatinib, they will respond to nilotinib, but not as well as could be expected. Dasatinib (70 mg) is usually prescribed when imatinib fails to work well. Nilotinib is usually prescribed when dasatinib doesn't work well along with other TKI drugs.

Imatinib was my first drug prescribed and it failed (although it did alleviate my symptoms by lowering disease burden somewhat, but not for long) in a similar fashion to your situation. I was switched to low dose dasatinib which worked immediately and ultimately enabled me to achieve treatment free remission.

Your goal is to achieve PCR < 1.0% by 18 months. You have time. Switch drugs and be vigilant. Make sure your vitamin D (blood level) is above 60 ng/ml so leukemic blast cells are less an issue (or no issue). Patients who achieve a PCR < 1.0% have over a 95% survival (and the other 5% tend to die of something else anyway).

 

Hi Scuba,

Thanks for your prompt and detailed reply.  My consultant would not
consider Dasatinib as I had a pleural effusion on diagnosis. It was
investigated and found to be due to my unchecked CML pre-diagnosis.  It
was partly drained, and is very slowly reducing since then, but the
consultant doesn't want to take any risks of it increasing again.

She mentioned Ponatinib as a possible option to switch to: how does that
work compared to Imatinib/Nilotinib?  And do you know what the typical
"side-effect package" for it is?

Look forward to hearing from you.

 

 

Hi Mary,

Not sure where you are being treated, but if your consultant is 'in a bit of a flap' then you/or your consultant could access the Hammersmith CML Expert team for advice. This service, is as far as I am aware, unique and open to all - patients and clinicians - not matter where you are. See the link on the pinned post at the top of this page or follow this link: https://cmlsupport.org.uk/thread/14289/hammersmith-hospital-ask-cml-expert

I was also diagnosed (over 20 years ago now) in late chronic stage with a (very) enlarged spleen - although my white count was only 17 - the size of my spleen alerted my GP and subsequent blood tests showed I was PH+. Fortunately I was quickly referred to Hammersmith who were at the forefront of CML even then, and still are. 

Apart from ponatinib - there is bosutinib, which might be better for you to try before ponatinib. I understand that this must be very worrying for you, but do reach out to the CML clinicians at Hammersmith. They are committed to helping patients (and doctors) get the right TKI for them.

Sandy

Hi there 

I’m really sorry to hear about the difficulties your having in your treatment. I really hope they get this sorted out for you so that you can get back on track..

I had two failed treatments, because I developed a mutation, they did work for a time, but failed when my levels got to a certain percentage, and the reason for that was the mutation I was moved on to Ponatinib which was developed specifically to target that mutation, I was a bit anxious having gone through the good news of the two other “tinib” treatments only to be eventually told they’d failed, but  this week  I’ve just had the 2nd blood test result that shows my Leukaemia level is now 0.002%! My doctor said that is a fantastic result, I agree 😊

he said he will lower the dosage in a couple of months, so there is hope, and assurance  that these treatments can and do get the results that they are designed for.

God Bless you, and everyone that is going through CML, with tributes and gratitude to the doctors and specialist who are involved in detecting treating and developing these new targeted treatments. 

 

 

Hi there 

I took 4,000 vitamin D3 for almost  2yrs  prior to my diagnosis, which happened as a result of an emergency hospitalisation for sepsis, in 2020, I believe my Vitamin D3 my Vitamin C with zinc may have played a part in helping me to survive that. 
my white blood cells where off the chart so where my playlets they said they’d never seen a blood test like mine in their entire career..

I stopped taking my Vitamin D3 and vitamin C with zinc this year as the summer had arrived, and a friend said that she saw that too high a dosage of vitamin D3 can cause hair loss..and my hair had changed texture to fizzy dry and thinner, I had a very itchy scalp as I remember, and I have seen some info on the connection with Ponatinib and hair loss, after reading your comment about Vitamin D3 I’m wondering if I should restart my D3 and C with zinc? 
 

I was also worried about the affect of vitamin D3 high dosage on the liver?

Can I ask my Doctor to check my Vitamin D levels? 

I was so pleased to hear you went into treatment free remission congratulations.

my Doctor said I’d remain on my treatment for life? 

 

Hi Mary 

Ponatinib worked very well for me I got a result of 0.002% in a matter of couple of months. 

Hi Norma,

I would restart Via D3 plus C and zinc if I were you. Re hair - thinning and texture. This can and does happen with age let alone health/treatment etc. However, since adding high dose magnesium to my daily Vitamin/mineral stack my hair has literally bounced back to it's former thickness and texture... I am sure it is because of magnesium. Sandy

You should most definitely have your vitamin D level checked. This can be done at your doctors office or if labs in the U.K. let you order your own tests and give you the results, you don't need to visit a doctor. It is a simple blood test.

One you have your result, you will know if you need to supplement with more D3 or with less. Your target range for vitamin D is between 60 - 100 ng/ml.

The target vitamin D blood level for cancer prevention and healing is over 40 ng/ml, but higher, between 60-100 ng/ml might be better.

Thank you 

yes my hair has been affected, Should I start back on the high D3 dosage?

at the moment I’m having horrendous problems with low back discs and hip I’m seeing a chiropractor, My GP (without seeing me) said it’s sciatica because the pain goes down my legs.

but I’ve had sciatica before and this is different it’s my entire legs, walking is particularly painful I have to keep stoping and going upstairs leaves my legs feeling strained and weak. 
I don’t know if this could be a side affect from the Ponatinib (peripheral Nuro) or to do with cardio vascular 

I will phone my specialist nurse tomorrow.

The pain in my low back hip and shin was like being hit with a hammer, it’s been unbearable for weeks, hardly any sleep my GP gave me anti inflammatories and some diazepam. 
 

my low back pain and hip are not as intense now, but my legs feel like I have a lot of inflammation down to my feet.. it’s not just when I walk now it’s there all the time.
Im hoping a lower dose of the Ponatinib will decrease my symptoms if that is what’s causing this. 
what’s your thoughts Sandy ? 

Thank you 

yes my hair has been affected, Should I start back on the high D3 dosage?

at the moment I’m having horrendous problems with low back discs and hip I’m seeing a chiropractor, My GP (without seeing me) said it’s sciatica because the pain goes down my legs.

but I’ve had sciatica before and this is different it’s my entire legs, walking is particularly painful I have to keep stoping and going upstairs leaves my legs feeling strained and weak. 
I don’t know if this could be a side affect from the Ponatinib (peripheral Nuro) or to do with cardio vascular 

I will phone my specialist nurse tomorrow.

The pain in my low back hip and shin was like being hit with a hammer, it’s been unbearable for weeks, hardly any sleep my GP gave me anti inflammatories and some diazepam. 
 

my low back pain and hip are not as intense now, but my legs feel like I have a lot of inflammation down to my feet.. it’s not just when I walk now it’s there all the time.
Im hoping a lower dose of the Ponatinib will decrease my symptoms if that is what’s causing this. 
what’s your thoughts Sandy ? 

Thank you for your reply, I’ll ask my GO for this test. 

Thank you for your reply, I’ll ask my GO for this test. 

Hi Sandy 

I forgot to add I’d been doing a lot of heavy duty work on my garden From May to early July. 
 

I started in a May but had to stop for a couple of weeks because my front and back thighs completely seized up, I went for a massage once the painful thighs eased up a bit..

I was doing a lot of heavy lifting too, so this could have brought on my back problem, plus I have a old spinal injury in my upper thoracic spine, which could be contributing because I had an MRI in 2020 when I went into hospital, although I did not officially get the results a senior nurse told me my 3 discs where still bulging and had scarring on my spinal cord. 
 

This could be the route of my problems now, I over did it in the garden trying to keep my mind occupied, plus I love my garden.

but I’ve had a problem with my legs down into my feet before I did all that work.. I will ask the specialist nurse to guide me on what to do to rule out that it’s not the Ponatinib.