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Have you reduced your dosage due to deep response? Share your experience

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Hello all

I'm looking for people who have reduced their dosage due to sustain deep response, because I would like to get a feel for how long people need to show deep response before its sensible to ask for a trial reduction.

In my case, I am aware that I'm jumping the gun here, I'm 10 months post diagnosis and got to a undetectable level after 9 months on 400mg Imatanib*. Yay!

Very early days yet but I'd like to read your story on this thread: What is/was your treatment? How long after diagnosis did you get to undetectable? How long did you continue with the same dosage? What  did you reduce to and briefly how did the reduction go?

I see this as different to the updates on the destiny thread, I'm looking for what qualified you for the trial more than what happened afterwards - Hope this makes sense to you.

 

*Note: I had a sub optimal response at 3 months but on track by month 6.

Hi,

That's quick, but not unwelcome for an undetectable response!

Do you mind me asking what lab that was done at? Not all are equal.

Much research is ongoing as to how long a deep response should be held before trying to stop taking TKIs. At CML Horizons last year the conversation was 2 years of a deep response was an appropriate time to consider stopping, but the data suggested stopping earlier might not be such a good idea. However, much of this data is just emerging and not every study will agree with others. And of course everyone is different, and what works for one person may not work for another - so it's not much consolation if you have held a deep response for many years and can't stop and similarly you won't care too much if you are under this 2 year threshold but manage to stop without incident. 

As with many things CML the real answer is "nobody is sure".

David.

All tests done in the Swiss Cancer Centre, not sure what lab is behind that.

Found a paper that suggests being female helps my chances of being able to maintain deep response with reduction/discontinuation. https://www.ncbi.nlm.nih.gov/pubmed/23515925

Hello Eva

I was diagnosed in 2009, and started on 400 mg imatinib as part of the SPIRIT2 trial.  After 5 years I came off the trial, and asked about possibly becoming part of the DESTINY trial.  Since Edinburgh, where I live, was not one of the centres for this trial, my consultant suggested that I might try a reduced dosage as my PCR results were good. Over the previous year they had reduced from 0.025 to 0.0071.  At that stage I went on to 300 mg, and was 'undetectable' after 6 months (though the next result was up).  In March last year I reduced again, to 200 mg, and although my results have gone up again a little (0.012 in December 2016), my consultant says I am still able to continue on this dosage.  This suits me well and I don't think I would be happy to try and reduce any further.

I hope this helps.

Olivia

I'm about 9 months after diagnosis, expecting my latest 9-month results in a few days (at 6 months I was at 0.37% - hoping to be below 0.1% this time, fingers crossed).  Was planning on talking to my doctor on Tuesday about reducing my Tasigna dosage from 600mg a day to 400mg... mainly because I'm having bad skin reactions.  Is anyone here experimenting with Tasigna at anything < 600mg a day? 

Hi Eva

It's my understanding that data from long running stopping studies show that only SOKAL score and TKI duration is predictive (potentially) of whether or not someone is likely to be able to stay off TKIs. Sex was investigated but not found to be relevant.  This was certainly part of the final report of the French STIM (Stop Imatinib) study, a link to which is in the Articles section under the Resources tab on this website.

For all stopping studies so far I believe there has been a requirement of both TKI duration and long term deep molecular response.  Bearing in mind the STIM report, that makes sense.  I am about to complete DESTINY (Dose reduction and stopping study) - I too reached Undetectable very quickly (6 months) - that was in 2009, and I went on DESTINY in April 2014, stopping completely in May 2015. My CML has not reappeared. I think for the French study it was 2 years undetectable but the requirements for DESTINY were less stringent. 

Good luck - you're in a good place and in time it looks, at the moment anyway, that you may well be able to try stopping in the future.

Best

Richard

 

 

 

Hi, I'm 6+ years after dx and have been stable MMR for 3+ years. I recently approached my consultant about dose reduction.  Although not part of a clinical study  my consultant was happy to reduce my Tasigna from 600mg to 300mg daily. They were satisfied with the results from both destiny and local experience of dose reduction and supported my request for dose reduction. I view dose stopping as unrealistic for me and my PCR frequency has been increased so we can monitor my continued response. 

Early days, but I've noticed a slight improvement in hair and skin, but energy levels broadly the same. I think that if I can sustain a response then half dose is no bad thing- I'd prefer my body to not process any more medicine than absolutely necessary, we don't know the long term impacts of Tasigna. I'm also acutely aware of the cost saving to the NHS.

 

Early days, so let's see what the results bring.

 

Chris

I was diagnosed in later September and started Tasigna 600mg.  Early side effects included headache, fatigue, cough, various GI issues, elevated glucose, bilirubin and ALT - none of these was serious and all have resolved except glucose (hovering around 115) and GI, although this latter issue is much better than it was.  Worse initial issue was skin cancer - see my post Skin Cancer - 7 and counting in 4 months. In late February/early March, I had a horrible bout of mouth ulcers, followed by swollen salivary glands, followed by less severe ulcers, followed by a second episode of swollen salivary glands, then another round of even less severe ulcers, a third and so far final episode of swollen salivary glands.  No more ulcers, but continuing dry mouth which seems to be very slowly improving. Even has a neck CT scan to rule out salivary stones or a tumor which was negative.  So even though my oncologist at Mayo Clinic isn't convinced this was caused by the medicine, I certainly am.

Now for the good news - my leukemia responded very quickly to the Tasigna.  I was MMR in 3 months and .006% IS on March 10.  The March 10 PCR was prompted by me approaching my oncologist about reducing my dose to see if that would help reduce the incidence of new skin lesions.  He said absolutely no way and I said it was the only option that I would consider because I was not ready to switch medicine yet.  So he reluctantly agreed and tested me immediately on March 10 and then again on April 5, when PCR showed <.003% IS, so somewhere between 4.5 and 5.0 log or about as close to undetectable as you can get while still being positive. Since the dose reduction, GI issues have improved even more, mouth issues have improved and continue to do so, and most importantly, incidence of new skin lesions has dropped significantly (also likely contributing to this is an improving immune system and a daily regimen of 1000 mg of Niacinamide).

I believe that we are all different - some people need more TKI and others less to achieve and maintain MMR and beyond.  I believe I am one of those who needs less and desperately want to try further dose reduction and do not at all mind more close monitoring.  I would like to go from daily dose of 450 mg now to 400mg, then 350 mg, then 300mg, then 200mg, then 150mg over the next 2 years or so. Unfortunatley, my oncologist is old school and says that further dose reduction is not possible until there is at least five years of clinical data from dose reduction trials like DESTINY.  He would allow me to stop if I meet the STOP trial criteria (3 years of therapy and 2 years of PCRU).  While I would love to be able to stop someday, I think it makes much more sense to gradually reduce in an effort to find the threshold level of medicine that keeps me below MMR while minimizing short and long term side effects.

I feel so strongly about further dose reduction now or soon that I have a consultation with Baptist MD Anderson here in Jacksonville FL on May 3rd to see if they are more open to this than my Mayo oncologist. We will see what happens. Dr. Cortes, who heads up MD Anderson's CML program in Houston Texas is a big believer in threshold level dose and regularly starts many of his patients on less than full dose and then either increases or decreases based on response.  I think this approach is the new frontier in CML treatment and one that is logical and safe if properly monitored.

The world of CML is full of patients and progressive oncologists who are trying dose reduction and it is working for many.  The forums at

http://community.lls.org/forum/27-chronic-myeloid-leukemia/

are full of these types of stories, so take a look.  Good luck whatever you decide.  It is your disease and your body and your life.

Hi Eva H:  I was diagnosed on 23 February 2009, and I was placed on 100mg of Sprycel - dasatinib.  My CML was undetectable by October 2010.  I had been in the accelerated phase at the time of diagnosis.  I went down to 50mg of Sprycel at least 3 years ago. Still undetectable. Now considering going down to 25mg or stopping taking Sprycel completely.  I did wait some years before reducing dosage despite being undetectable. Hope that helps! Philip

Thanks All for your replies so far - Please do keep them coming. 

Its really useful to see when the potential light at the end of the tunnel might come :)

Hello Olivia, I was diagnosed in 2009 as well. After initial treatment I was put on 100mg of Sprycel.  Condition undetectable since October 2010.  Reduced to 50mg of Sprycel about three years ago, at least. My condition is still undetectable. Now considering stop taking Sprycel by the end of the year. Philip

Hi Richard:  I was very happy to read your post. I will have been undetectable for seven years this coming October after reducing dosage to 50mg of Sprycel a day for over three years now. I'm very excited thinking about possibly stopping drug therapy at the end year!  Philip

Hi Eva,

You might be interested in this article which links higher levels of NK (Natural Killer) cells to MRF (molecular relapse-free) survival after stopping imatinib. 

Sandy

Hi, Chris and Cmljax,
I am also interested in dosage reduction due to deep response. I was diagnosed in Sept 2019 with BCR_ABL at 33%. I’ve started treatment with Tasigna 600mg per day. I was really lucky to be a fast responder - BCR_ABL was: in Jan 2020 – 0,052%, in Apr 2020 0.0019% and in Jul 2020 < 0.0006%.
I feel that this dosage it too high for me and I could continue with a lower dose. I passed through many side effects: low WBC and neutrophils, diarrhea, rash, hair fall, eyebrows fall, fatigue, muscle and joint pains, cough, high bilirubin, high liver enzymes, creatinine constantly goes higher and is at the upper level of the norm now… All side effects were relatively mild to middle.
I’ve talked with three oncologists about dose reduction but their opinion is that it is too early.
Before talking with them and after I saw my result in April, I reduced my dosage to 550mg. With this dosage in July the result was < 0.0006% (undetectable). Based on that I reduced my dosage to 500mg.
Even with this small reduction I’ve noticed improvement of side effects.
Now I am afraid to make further reduction. Doctors said that their concerns are possible development of resistance and mutations. On the other hand I really want to keep my liver and kidneys and to reduce side effects as much as possible.
Could you please share your experience with further dose reductions during the last 3 years (after your posts)? What was the criteria for staying on the lower dose – keeping MMR or keeping the achieved result? In case I am MR5 and go the MR4.5 or MR4, shall I increase the dosage? In what increments did you reduce your dosage – 150mg, 50mg? How often were you tested? I also think it makes much sense to gradually reduce in an effort to find the threshold level of medicine needed.
Any knowledge and experience would be very helpful for me and for other people on this forum.
Good luck to both of you and stay healthy

You can absolutely consider lowering dose from 600 to 300 mg tasigna. I know several patients in your situation taking tasigna who did just that with no change - except their side effects lessened considerably.

You wrote, "Now I am afraid to make further reduction. Doctors said that their concerns are possible development of resistance and mutations".

Your doctors are misinformed with outdated thinking. CML is not a virus or bacteria - that is where this nonsense comes from. Any mutuation(s) in CML you either already have (smoldering) or can form spontaneously* and have nothing to do with your current drug. You want the right drug at the lowest dose which works. Finding the lowest dose which works is personal to you (customized). Careful PCR monitoring is used to find this dose. In your case, you may not even need any drug! (wouldnt' that be nice), but it will take a few years at "undetected" to reduce the clonal population where TFR has a chance of success.

Your drug either works on the clone you have or it doesn't. If a new clone emerged for which your drug does not work, no amount of dose would matter and you would need a new drug. And if you lower your dose and CML increases, you can always increase dose. This helps you find the correct dose.

(*and with diet modifications you may be able to suppress immune weakness so any new mutation never sees the "light of day" and is handled naturally)

 

Hi, Scuba,
Thank you very much for your answer. Your opinion is of very high value for me. I have read some of your posts in this forum and you always give a great amount of valuable information in a way people to understand you. I also read the two articles for which you gave me links.
My concern is that the trials referred in both articles include patients who were at least 3 years on full dose TKI and at least 1 year on MR3 or better. My case is only 10 months on TKI and 7 months on MR3 or better. I even started a slight dose reduction on my own decision on the 7-th month of therapy (which is month 4-th on MR3 or better).
Have you come across an article for dosage reduction for newly diagnosed people who respond fast to the therapy?
Currently I make PCR tests every 3 months. In case I consider a further dose reduction what is the best moment for this – 6 weeks before next PCR? As my doctors do not recommend dose reduction, I cannot make PCR tests more frequently.
What will be the criteria for staying on the lower dose – keeping MMR or keeping the achieved result?
I am MR5 – if I go to MR4.5 or MR4, shall I increase the dosage?
What diet modification you would recommend?
Thank you very much and be healthy and happy!smiley

  • Have you come across an article for dosage reduction for newly diagnosed people who respond fast to the therapy?

I have not read any articles in response to your question. Most patients have their dosage lowered due to side effects and then doctors noticed no change in response and in the case of dasatnib, some patients had improved response (on lower dose).

 

  • Currently I make PCR tests every 3 months. In case I consider a further dose reduction what is the best moment for this – 6 weeks before next PCR?

When a dose is changed is is a good practice to test at six weeks. However, if a patient has no blasts, the time it takes for CML to build is slow. CML is a slow disease when in chronic phase. This is why protocols have emerged for women with CML who want to have children. They can stop therapy for nine months, CML will often  rise by several logs, but then after birth when they resume therapy they return to pre-pregnancy CML levels. I know one patient personally who has done this (and delivered healthy twins).

  • As my doctors do not recommend dose reduction, I cannot make PCR tests more frequently. What will be the criteria for staying on the lower dose – keeping MMR or keeping the achieved result?

Maintaining a current result is minimal. If CML rises by more than 1/2 log, odds are low dose is insufficient. This is certainly the case with imatinib which is very much dose dependent. Testing a lower dose is just that - a test. If it works, great, if not, then resuming original dose should bring CML back in control. I have come across no research documenting permanent loss of response when a patient resumes normal dose following lower dose. In fact, the DESTINY trials document very well that stopping, starting, dose modification are very effective with minimal (to me it reads: zero)  risk of progression in managing CML.

  • I am MR5 – if I go to MR4.5 or MR4, shall I increase the dosage?

At MR5 (which is excellent), a rise of 1/2 log (MR4.5) would be a concern, but may not trigger a dose change, I would wait one more cycle to see if the trend continues. Again, at MR5, you have very low residual disease and even if CML starts to expand, you have time to "experiment".

  • What diet modification you would recommend?

Search this forum and other locations for posts on vitamin D, magnesium, vitamin C, vitamin K2, Keto, quercetin. ln general you want to improve your diet favoring a very strong immune system. Supplement as necessary.

Hi Scuba,
Thank you very much that you were so kind to answer all my questions. I will continue to read and educate about CML and will share my experience with further dosage reductions.
Wish you good luck and health!

Hi, Eva,

if you don't mind could you please share your experience with dosage reduction? I am in the same situation in which you were 3 years ago (my posts are below in this conversation). Your experience will be of great help for me and for other patients in this forum.

If there are other patients who have reduced their dosage due to deep response, please share your experience.

Thank you very much in advance to all of you!smiley

Lucky

Hi Lucky,

I reduced my dose of dasatinib from 100mg, down to 70, then 50, and finally 20 over maybe 18 months or so to reduce side effects. My doctor is maybe more cautious than some others, and given a few other things in my life we decided a slow and steady approach was best. While PCR numbers always bob around, my results have stayed very low and never rose to a worrying level. In fact, my test just last week came back at exactly MR5. A single positive assay in 138,000 - my best ever.

David.

That's great to read, David! Congratulations.

Focus on getting rid of those remaining leukemic stem cells and  "undetected" is in your future!

(Selenium, Curcumin, vitamin D ... you know the drill)

Hi David,

many thanks for your reply and congratulations for your so good result!

Did you do the dosage reduction during the first 18 months after diagnose? In what levels were your results during that period - MR4? MR4.5?

Wish you all your next tests to be undetectable!

I reduced my Tasigna doze from 600 mg to 300 mg, because of sidde effects, i was im MM3 for about 4 years, never reach MR4, untill now laugh.

Before reducing BCR ABL was 0,03, then after 3 months on half doze- 0,01, after 4 months 0,008. The only change i do its added 4000 iu/day of D3 with K2 after i read Scuba post (thank you Scuba by the way), and some curcumin.

I hope will by lesser next time.Thank you all for this forum,you helped my a lot.

No, I had been diagnosed for about 6 years before reducing dosage. I started reducing at MR4.

David. 

Hi Scuba,
I looked at the references of the articles you sent me and found a good news for patients who are on nilotinib: “Switching from nilotinib twice daily to once daily at a reduced dose does not compromise clinical activity among patients with chronic myeloid leukemia (CML) who have a major molecular response (MMR), according to data presented at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.
Primary reason for the switch to a reduced QD nilotinib dosing was non-serious adverse events in 37.3% of pts and improvement in pts convenience in 62.7% of pts. Median duration of nilotinib prior switching to a reduced QD dosing was 29 months (range: 1-94) and median duration of MMR was 25 months (range: 3-212).
I think this will be useful for patients who are thinking of dosage reduction:

Lucky