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Confused - treatment change



I’ve been reading posts since my wife was first diagnosed with CML (chronic phase) in November of last year, but this is my first post. 

Today, my wife’s dr indicated that her treatment would be changed from Dasatinib to Nilotinib over concerns she wasn’t responding to Dasatinib, and I’m not certain this is the best course of action. I added as much detail as I could below (apologies for the length).

 Please let me know your thoughts, should we look for another opinion before switching treatments?



My wife was started on Dasatinib in late November 2019 - 100mg.  After approx 3 weeks, both her neutrophil count and her platelet count were too low to continue treatment and she cycled off.  This lasted about 3 weeks before she resumed treatment, but at 70mg.  

She was taking the 70mg for 4 days before having to cycle off again due to low neutrophils and we went to see her dr 3 days later.   Her blood counts during the visit (4 days after the previous test) were normal and the dr believe the previous test results might have been erroneous. Regardless, my wife’s dose was lowered to 50mg and a PCR test was ordered.   Mind you, my wife was only actively on Dasatinib for 25 or so days over the course of 2 months (3 weeks on, 3 weeks off, 4 days on, 3 days off). 

Results came in today and showed little to no molecular response.  For me, these results were not surprising as she was off Dasatinib more than she was on Dasatinib during the last 2 months, and it had been several weeks since she was on the medication for any meaningful length of time. Also, the literature I’ve read and data I’ve reviewed suggest the indications for MMR/DMR can be observed at 3 months (found one article that looked at 1 month as an indicator, but I haven’t found any supporting articles yet for this correlation study) AFTER being in the medication for the entirety of those 3 months.  

Her drs concern is that my wife might not respond to Dasatinib and she is not comfortable with continuing on Dasatinib at 50mg - she would have been ok staying on Dasatinib, but at 100mg (which dropped my wife’s counts and started the cycling). I’ve also read that lower doses of Dasatinib have shown to be as effective as higher doses, but with fewer side effects. 

The proposed plan is to switch to Nilotinib at 300mg 2x/day.  However, based on my wife’s data, existing literature and my wife’s inconsistent treatment over the last 2 months, I’m concerned the decision to switch is premature and out of an abundance of caution.   

I do understand that my wife my react better to Nilotinib and might experience fewer side effects (she has bad headaches in the morning - sorted but some coffee - and fatigue can be an issue, plus the drop in neutrophils and platelets), but quick decisions with minimal / incomplete data are flags for concern for me.  

I agree that there seems to be a lack of data and history for making a switch so soon in treatment.  If you can visit a CML specialist/researcher, then that would be beneficial.  Is her doctor not aware of the research exploring the 50 mg dose as initial treatment?

My doctor repeated all of the diagnostic tests at three months.  It seems a little early to be using PCR results as the basis for treatment decisions.  Do you have any FISH (Fluorescence in situ hybridization) test results? 

Hi, I am on 50 mg Dasatinib I refused to go on 100 mg because it's too toxic it can cause so many problems .Make sure your wife drinks enough water stay hydrated headaches will disappear .I would say stay on 50 mg and give it a chance to work your doctor is in such a rush to change meds he's probably not a CML specialist .Its easy to take just before bed where as I think you have to fast and take it twice a day on Nilotinib .Dont be bullied into changing meds give it a bit more time ,and change your doctor if you are not happy with him.Try not to panic hopefully your wife will settle down and respond well ,life will be normal .Good Luck , Denise.

Thank you both for your responses and insight.  I need to find her FISH results - this test was performed when she was first diagnosed.  From what I recall, the BCR-ABL1 mutation was confirmed with 96% of cells showing the mutation.  

My wife’s dr has been very active with CML, but I believe focuses more on ALL/AML now. This was one of the reasons we chose this dr. 

We plan to see another CML speclist who is currently active with studies and research.   

Your wife's situation and response mirrors mine almost exactly.

I had to stop taking dasatinib due to severe myelosuppression - very low neutrophils, platelets. But my doctor, who was one of the top four CML researchers in the world was "pleased"! He told me that in his clinical research he noted those patients who responded with blood suppression (i.e. neutrophils) often ended up responding to dasatinib the best with very deep molecular response. His approach was to keep "cycling" me on and off dasatinib. He started me at 70 mg one time, then dropped me to 20 mg straight away. Even at that dose, I still had to stop therapy due to myelosuppression, but he continued to keep on this path of a very low dose of 20 mg until my body adjusted. And it certainly adjusted. What was happening, he believed, is that the CML cells were getting killed off dramatically leaving a "hole" for my normal blood system to fill. That takes time - months and months. It took me 3 - 4 cycles (on then off) and 9 months before my blood counts stabilized. My leukemic blood system was getting replaced by my normal blood system. During this phase, my PCR hardly changed.

Once I was able to stay on drug consistently - my PCR percentage plummeted.

I am now "undetected" and have been for almost 3 years while taking only 20 mg dasatinib. No side effects I can feel.

My strong recommendation to your wife's doctor is to stay the course - drop dasatinib dose even lower to 20 mg in order to get a baseline (i.e. so she can stay on drug) and there is a strong likelihood she will never need to increase her dose. More than likely, she will experience a deep response.

As long as her blast cell count is near zero - she has plenty of time to get this right.

Keep us posted if this is what she elects to do and her progress. It would be nice to get more data points so others don't suffer mistreatment. Too few doctors know that lower dasatinib dose in the face of myelosuppression is a better course to follow.


Thank you, Scuba - your response was very helpful and reassuring.

Currently, my wife seems to be tolerating 50mg of dasatinib relatively well.  Her panels look great at the moment on 50; however, to be fair, she has only had 3 doses prior to the last set of blood tests.

This morning we received the actual data from the PCR test and, after review, the data is even less conclusive as her result was above the upper limit of quantitation, which is 50% BCR/ABL1 for this test (the result was reported as "High positive, unable to quantify"). 

While, yes, this is aligned with her initial PCR test, this result (and this test for that matter) provides absolutely no value in assessing response to dasatinib.  Had I known the LOD (limit of detection) for this test yesterday, I would have pushed back much harder during our discussion - I am upset with myself for not reviewing the IFU for this test.  There is no way for this test to accurately determine a molecular response due to the low upper quant limit.  My wife's % could have dropped from 96% to 80%, 70%, 60%, etc.  

We do have an appointment next week with another leading CML physician and will discuss all of this with him.  I am hoping that she can remain on dasatinib at 50 until there is a clear indication that a change is necessary.    




If I understand your situation and concerns correctly, I suggest you take a look at our PCR booklet which may help you when trying to understand your wife's test results. 

At diagnosis, a Qualitative PCR test will confirm that the diagnosis is correct.... i.e it is used to as a Yes or No. After TKI treatment starts, the tests that are most useful are cytogenetics and/or FISH. Cytogenetics test around 20 or so cells whereas FISH can test upwards of 200 cells from any one sample. Given that most of us are diagnosed with quite a lot of leukaemia (Ph+ cells) in our blood/marrow system such a sensitive molecular test like Quantitative PCR is not accurate enough to be of use. This is why FISH testing is used to assess response to therapy, at least until the  Ph+ cell population is reduced to less than10%.... at this lower level Q-PCR can them more accurately measure at the molecular level. 

Below is a snip from our Q-RTPCR booklet, which you can download by clicking on the link below or on our home page. If you are in the UK and would like a hard copy of the booklet, then please contact us with your address and we can post a copy to you. Take a look at pages 8 and 9 which gives an overview of the tests used at different stages from diagnosis onwards. Pages 11 and 12 may also be helpful to read.

I hope this is helpful.


Quantitative PCR (q-RTPCR)

'At diagnosis, virtually every white cell in a blood or marrow sample will be leukaemic (Ph+) so the result should, in theory, be 100% Ph+. However, because there are higher levels of Ph+ cells present at diagnosis, q-PCR testing is not accurate, which is why Ph positivity varies between 50% and 100%. This test may be used to establish a baseline value of Ph+ cells at diagnosis.

After the start of therapy q-PCR is used at specific time points after cytogenetic/FISH tests. Once tests show that the Ph+ cell population has reduced to less than 10%, q-PCR testing can more accurately quantify the amount of residual disease left in the marrow.

The goal of TKI therapy is to reduce the abnormal BCR-ABL1 gene to a deep molecular level, preferably to at least 0.1% (MMR/MR3).
During the first 3, 6, 9 and 12 months of therapy Ph+ cells should reduce significantly. When the level of Ph+ cells falls below 1% q-PCR testing is extremely accurate and will be used to monitor the stability of a molecular response. Under ideal conditions, this test can detect
1 Ph+ cell in every 100,000 cells, although more commonly it detects 1 Ph+ cell in every 10,000.

Thank you Sandy for clarifying / confirming my assessment.   

I do not know why a PCR test was ordered when my wife was only treated for a total of 24 days spread over 2 months.  There was little chance my wife’s BCR/ABL % would have dropped into the appropriate range for the PCR test AND the last time a FISH test was performed was at diagnosis.  

So we saw (and are switching to) Dr Mauro last week and he agreed that my wife should continue on Dasatinib @ 50mg.  We will do another PCR test in 6 weeks, which will be 2 continuous months on Dasatinib.  Thanks again everyone for the advice.   I’ll keep you updated on progress.