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18th month PCR RESULT , A Blip and Next Step ?

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BCR-ABL (IS)

54.61  Oct 2015  DX

1.088  July 2016 ( 9 th month )

0.116  Oct 2016 

0.030  Jan 2017  

0.152  April 2017   ! Lost MMR !

0.065  May 2017

0.085  Sept 2017

0.046  Dec 2017

0.041 April 2018

0.018 August 2018

 

Gleevec

400 mg 28 October 2015  - 26 November 2015

300 mg 26 November 2015 - 23 January 2018

200 mg 23 January 2018 to present

+

* 16-24 March 2016 stopped due to neutropenia

* 200 mg 24 March 2016- 07 April 2016

* 300 mg 07 April 2016-28 April 2016

* 200 mg 28 April 2016 - 23 May 2016 200 mg

 

Hi to All , 

i will be happy for any recommendations or suggestions . 

------------------ Just a Summary ---------------------------------------- OPTİONAL TO READ

my mother is a cml patient since 28/10/2015 ( started Glivec 400 mg ) . she is 69 years old , 150 cm and 58 kg (  relevant to her dosage i guess )

Summary of her dosage first year is

1-After first month her dosage set to 300 mg .

2- approximately 40 days she didnt take her medicine ( due to several UTİ's and her idea of drugs was making her that way ( nausea and vomiting from UTİ )  

3- didnt take medicine due to neutropenia for two weeks . then started 200 mg for two weeks then back to her normal dosage 300 mg. 

with all this handicaps her PCR results for the 12th month was % 0.1164 ( IS) 

she has been and feeling good since 11 th month . no more UTİ , no more vomiting and nausea . 

Puffy eyes and .

1 her renal functions are dropping but she is not in a serious situation . 

2 anemia 

are her side effects . but still we are happy with glivec at least for last 7 months.

------------------------------------------------------------------------------------------

Our last 3 PCR Results are below ( all tests are from peripheral blood (her arm) and in IS )

12th month ............%0.1164 ( IS )

15th month ............%0.0306 ( IS )

18th month ........... %0.1522 ( IS )   04/04/2017

my questions 

1 - From what i read so far , this rise may be from an update or calibration in the lab. ( first thing to ask monday ) if this is the case i guess she is going to use same dosage (300 mg ) and wait for the result of her 21st month PCR test . 

2- whether it is lab or not , should we wait for 21st month PCR ? i mean maybe another Pcr test or CBA  , mutuation tests as soon as possible ? 

3- she never gave blood from bone marrow . all test are made from peripheral blood . even her cytogenetics . Fish tests were made just two times . first was at the diagnosis ( % 41 ) and the second one was at the 3rd month ( due to lack of PCR test ) which was % 0 .

any opinion what will be our next step and when it should be done ? i read most of the pdf s i got about follow up and monitoring and neither of them gives a specific time at warning or failure situations. 

english is not my native language . it was exhausting but finally i finished it .

all answers will be appreciated. 

her PCR Test are 

i am not sure about image.uk but first one is safe to use in turkey 

http://hizliresim.com/8MoW57

https://www.imageupload.co.uk/image/Baiy

no answers :( 

i am gonna update our situation for other patients and their relatives . 

yesterday we had our meeting . doctor told us their gonna make the other PCR test and fish test 3 months later .  i felt uncomfortable with this solution . and talked about procedure .which is according to 

this link 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915804/

'' It is important to realize that it is not unusual for PCR results to fluctuate up and down over time, in part because of laboratory technical reasons. If transcript levels have increased >5 times in a single follow-up sample and MMR was lost, the test should be repeated in a shorter time interval, and patients should be questioned carefully about compliance. ''

also other resources state similar solution. so we are gonna make a test in 4-6 weeks . they seem eager to change drug but we don't. i think i am gonna need another consult . so i am searching another doc . and want to hear what he/she is going to say about our situation.

best wishes to you all.

 

 

 

Hi there,

Is there a reason why she was reduced from 400mg to 300mg? 400mg is the "standard" dose for imatinib, so a lower dose could be part of the reason why she has not at MMR (0.1% IS) right now, but her 15 month result was in that range so that is good news.

If it was to reduce side effects, it may certainly be worth looking at another TKI. If it was to manage the neutropenia and other issues, maybe another TKI would suit better. She may fare better with fewer side effects. Out of interest, when she takes imatinib does she take it with or without food? Timing it right can make a big difference. In my experience, I felt unwell taking imatinib on an empty stomach but was much better when taken with food at lunch time.

Many oncologists don't take bone marrow biopsies now. PCR results from peripheral blood are excellent quality in most cases, and there is not always the need for tests on marrow cells. Taking a bone marrow sample may be needlessly invasive especially when the PCR result is trending the right direction.

If you are concerned about her PCR, and side effects of imiatinib howcome you seem so keen for her to stay on the drug? A change might work really well, and if it doesn't you can always change back.

David.

Hi David ,

Thank you for your interest and response . 

This took longer than i expected so i am gonna make this post as an interview. Q and A are enough to read.

Q : Is there a reason why she was reduced from 400mg to 300mg?  A : vomitting and her blood test results indicates 400 mg suppressed her values too early. but maybe we will talk about to go back 400 mg if the PCR results ( 4-6 weeks later after the 18th month ) shows a little raise ( no more than %1 ) 

when my mother first diagnosed she started with 400 mg.  before the start of treatment 

test results          WBC 44.4  / NEU 40        /  PLT 456. After the first month her values dropped to

                             WBC 3.33 /  NEU 1.730 /  PLT 154

at 400 mg , i am not sure but she vomitted  4 or 5 times within the first hour after she took her pill. 

maybe it was just pyscological or a adverse reaction.

as you see she had no Neutropenia or Thrombocytopenia but doctor seem to be anxious. and dropped her dose to 300 mg. 

at 300 mg , she never vomitted perhaps her body just adjusted itself . also her values got in normal range in 2-3 month .so we kept going on @300 mg. 

i mentioned my mother's weight and height . she is a small person like japanese people . According to this study 

http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2012.02253.x/pdf 

In conclusion, the long-term follow-up of the JALSG CML202 study revealed almost similar excellent outcomes to those of the IRIS study and others. There were no significant differences in OS and EFS between the 300- and 400-mg imatinib groups. However, cumulative rates of cytogenetic or molecular responses in the 300-mg group were inferior to those in the 400-mg group. The results of the present study suggest that imatinib at a dose of 400 mg may be optimal for Japanese patients, but that 400 mg imatinib is not tolerable in a considerable number of patients, and that the measurement of Cmin is useful in finding the optimal dose, especially in elderly and/or female patients. Nevertheless, excessive dose reductions to <300 mg imatinib should be avoided even in patients who are intolerant to 400 mg imatinib or have a small body size. We hope our findings are useful for the treatment of CML patients in other Asian countries.

 

 

Q : Out of interest, when she takes imatinib does she take it with or without food?  A: She has been taking her medicine after breakfast  with 300-400 ml water as suggested . ( every day )  

Q : If you are concerned about her PCR, and side effects of imiatinib howcome you seem so keen for her to stay on the drug? 

A : İ was happy until the last PCR result . If that raise keeps going and / or passes %1 she will change TKi. but new TKİ s are totally unknown to us. and that's worrying. and their side effects seem more scarry.

     Due to Urinary tract infection vomiting , nausea and loss of appetite were her real problem that effects her quality of life. that effected her too much in the first 11 months . (during 3-4 days, 7or 8 times) no UTİs at last 7 months .

     Last 7 months , my mother has only 2 bad days . the bad one was Loss of appetite , vomit one time but  the day after she was ok .

    She never experienced (except the 2 day , mentioned upper sentence) any side effects like tiredness ,bone / joint pain , cramps , diarr... etc .

   We are really happy with 300 mg gleevec . Her quality of life is very well.

   Also it seems ridiculous to say that but it is not an economical issue.  

  İn Turkey , gleevec has generic brands . but tasigna and sprycel don't. bosu and ponatinib have a bit different procedure to get i guess. i am not sure.

 So if you want to use gleevec , insurance pays most of them but you still have to pay like 90 GBP for a box. ( a percentage of the difference between the lowest priced imatinib and gleevec )

  if you use other two , you dont need to pay any money . insurance pays all because they have no generics.

    

 

About the other adverse reactions 

nausea and vomiting

i think i need to write it again.

From the start of her treatment  28/10/2015 to 29/09/2016 . her first  11 months was bad. she had urinary tract infections 7-8 times.

her ct scans , ultrasounds showed no problem. 

she is using her own wc . and its cleanliness is not an issue . we are both neat and clean . 

her personal hygiene - showers and changes underwears daily.

so there is no answer to why was she keeping that infection . most of the doctors said because of her immune system.  and for the last 7 months she never got it again . ( Her pcr at 9 months was %1 and 12 month was %0.11 ) so they were right about it i guess. we were thinking to change tki after 12 month pcr result and if uti happens one more time. ( UTİ is a very rare side effect of imatinib )

nausea and vomiting were related to UTİ ( urinart ... infection ) . last 7 months no UTİ no nausea and vomiting

 

renal functions  

according to this research 

http://www.cancernetwork.com/chronic-myeloid-leukemia/tkis-have-kidney-e...

yeap other tkis will be better choice but as i said before at this point it is not critical and it is under control . She is CKD 3b.

 

anemia

last test results RBC 3.35       range 4,06.......5,63

                            HGB 9,67       range 12,5......16,3

                            HCT 29,48      range 36,7......47,1

her anemia seems to be just on paper . no symptoms of anemia in real life .  

 

 

Ah, OK - I think I understand.

Since she otherwise gets on well with imatinib, if it controls her PCR well then you are keen to stick with it. Your doctors seem to be more "aggressive" in looking for a switch to another TKI because it (at 18 months) was higher than optimal - moving from 0.03% to 0.15% in 3 months. I imagine their rationale is that she achieved, and then lost MMR. 

For what it's worth, my own PCR was 0.13% at 12 months, 0.37% at 14 or 15 months, then back down to 0.13% at 18 months. From there, it continued to drop (as an overall trend) with several ups and downs on the way, and it is now around 0.02%.

Given your mother has lost MMR, it's probably a good idea to try to regain it as soon as practical. A 2nd generation TKI may be a way to do this, as her doctors suggested - but this would be on the basis (as far as I can see) of a single result which I am not convinced is enough data. Many of us have had several jumps up, which are followed by a similarly sized drop - I have had many myself, but must admit once I gained MMR I managed to retain it. 

David.

david hi and thanks again 

yeap , your last message summarize all our history and dilemma.

not having MMR ( 18 month or later ) but if your trend is going down this is not an issue . on the other hand losing mmr is a deal breaker i guess.

i am waiting a message from a similar patient (turkey) , translation of her message .

- @13 month her bcr abl raised from 0.08 to 0.10   her doctor thinks there will be resistance to imatanib. and doc is going to make biopsy (mutuations ? which test unknown ) to choose which 2nd generation TKİ she is going to use . 

as you stated in your message in turkey 

doctors seem to be more "aggressive" in looking for a switch to another TKI

 

will be updated but my plan as today 

04/05/ PCR and fish test ( 19 month )

18/05/ PCR result 

22/05 meeting with same hospital

after 22 / perhaps meeting another doctor ( according to her result and doctor's response )

 

best wishes

 

 

we made a small change to our program . 

23/05 meeting with doctor  (was today)

23/05 or 29/05 PCR test  - as soon as i convince my mom to go to hospital again.

12/06 PCR Result and showing it to doctor(s) then we will see what to do next .. 

 

 

i got the last result for PCR test today. and i guess the test of april was just a technical or lab sourced raise . not so good but definetely not bad. we are on track again .

29/05 gave sample for PCR 

13/06 result ( 580 day from the start of our theraphy )

% 0.0654 ( IS ) 

 

best wishes to all .

 

maybe this will be useful for other patients , especially if they were just searching just pcr results for a relief like me months before . i will update after every test.

05/09 22nd month %0.08 :(   but still in mmr

 

just an update ,

 

dropped dosage to 200 mg since 23 rd of  january 18

 

CML diagnosed October 2015

Essential Hypertension diagnosed 2014

Osteoporosis

CKD since March 2016

İron defiency Anemia diagnosed July 2016

 

BCR-ABL (IS)

54.61  Oct 2015  DX

1.088  July 2016 ( 9 th month )

0.116  Oct 2016  

0.030  Jan 2017   

0.152  April 2017   ! Lost MMR !

0.065  May 2017

0.085  Sept 2017

0.046  Dec 2017

0.041 April 2018

0.018 August 2018

 

Gleevec

400 mg 28 October 2015  - 26 November 2015

300 mg 26 November 2015 - 23 January 2018

200 mg 23 January 2018 to present

+

* 16-24 March 2016 stopped due to neutropenia

* 200 mg 24 March 2016- 07 April 2016

* 300 mg 07 April 2016-28 April 2016

* 200 mg 28 April 2016 - 23 May 2016 200 mg

 

 

Congratulations - that result is well into MMR territory! Excellent news.

David.