13 replies to this topic

[Ray99]

Just got the most recent PCR results and it increase to .17% from .11%.  I am a little concern that I might not reach MMR in 18 months, a NCCN CML guideline for optimal response.

I have been on Tasigna 300mg twice daily since diagnosed in April, 2012.  The response is great for the first four months and then it stalled.  The PCR for the following 11 months range from .3% to .1%

I understand from Trey's comments about Tasigna PCR plateau.  Has my PCR plateau lasted a little bit too long, almost 11 months?

My onc was considering switching me to Sprycel 70mg about six month ago.  We have discussed it in the last two visits.  But each time, he said that we should wait since the PCR did not increase that much.  I am seeing him next week and will know what he want to do this time.  I have little side effect with Tasigna and QOL is good.

I would appreciate any opinions, comments and advises.

[CallMeLucky]

If you could tolerate 400mg tasigna, I would try that before switching.  Also not clear why you would go to 70mg.  100mg is standard dose.

[Ray99]

Lucky,

   I did mention about 400mg Tasigna to the doctor in my last visit, as you suggested.  But he said that data does not shows 400mg is any more effective than 300mg.  I really don't know any studies has shown that.  As to why 70mg Sprycel, he said that since I am pretty close to MMR, 70mg should be good.

   I will ask him again next week when I see him.

[Trey]

This is one of those cases where there is no wrong answer given the information you have at this point.  You are very close to MMR, and these things are not that precise, either the PCR itself or the 3 log measurement.  You could stick with Tasigna, either at current dose or increase to max dosage (800mg/day).  Note that studies average out the responses, so some people have faster responses on higher dosage, but not the "average" CML population.  You could be one who could have a faster response, but maybe not. 

Overall there is no reason to change what you are doing except if it makes you feel better about "doing something".  Sometimes that is important, even if not entirely necessary.

[CDW]

Ray,

i've  been on 300mg Tasigna for 30 months and my best result yet is a 0.05% - I bounce up and down around the 0.1%-0.2% mark it seems. Per Trey's remarks your response is fine; not breaking any records, but fine. Its only natural to want the best possible response and i aimed for that initially. My view has changed a little since then as i've learned to cope with the ups and downs and not progressing per guidelines. I tolerate the drugs well, i can get hold of them with no problem (sprycel or Iclusig would be more difficult), QoL is fine and my response is ok.

MMR used to be the gold standard for response and is still seen by many oncs as a benchmark for a successful treatment. Unless my numbers change significantly i.e. sustained upward trend tending to 1% then i'll stick with my option and accept i may only see a 3 log response in the medium term and maybe 4+ log in the longer term.

In the words of my onc "your result is ok, not great, but very ok"

Chris

[Ray99]

Trey, Lucky, Chris

   Thanks for your suggestions.  Based on your comments, I probably would stay the course for now.  I will find out what my onc's opinion is when I see him next week.  I have been very keen to reach MMR before 18 month, as the NCCN guidelines stated. 

   But from the discussions on this board, it seems that CcyR is the most important milestone, which I reached in four months.  It may be good enough to hovering slightly above MMR.  I am leading pretty much the same life style as before I was diagnosed.  That is something to thank for.  I am at ease now and only hope that in the future there will be one zero after the decimal point in the PCR reading.

Ray

[Ray99]

I just came back from a visit to my doctor.  Recall that I have fast drop of PCR for the first four months, followed by a flat reading hovering around .3% to .1% for eleven months.

He thinks I must have some colony of BCR-ABL genes that do not respond to Tasigna.  That is why the PCR readings stay flat.  He has not seen that long a plateau among patients he treated, the reading either goes up or down and not flat for that long.  He gave me two choices.  Stay the course as long as PCR stay flat around .2%.  Or switch to a different TKI.  He is also agreeable to increase Tasigna dosage to 400mg.

If I decide to switch TKI, he will do a BMB, get a mutation test and then decide which TKI to switch to.  He will find out which Lab to send BMB for the mutation test.  It seems that he has not done that for a while. 

Any comments on my doctor's assessment?

Does anyone have any Labs to recommend for mutation test?

[Trey]

The Kinase Mutation Test is not sensitive enough to be useful at your PCR levels (near MMR).  The test only works at the same levels as FISH, which is approximately above CCyR.  So that would be a waste of time.

Regarding your Onc saying you may "have some colony of BCR-ABL genes that do not respond to Tasigna".  All TKI drugs fail to directly kill the highest level leukemic cells.  More likely your high level leukemic cells are trying to keep up with the Tasigna, which continues to kill off their offspring.  I have speculated that this is a possible (emphasize possible) cure process, to exhaust the high level leukemic stem cells so they die off trying to keep up with the TKI drug.  I don't know, but neither does anyone else. 

So there is nothing wrong with doing what you are doing as long as your plateau stays at such a low level.  Or you could increase drug dosage if you want.  Personally, I would not switch drugs if you like the Tasigna side effects profile. 

[Ray99]

Trey,

  I am leaning toward increase the dosage of Tasigna and see whether it would further lower my PCR and, most importantly, if I can still tolerate it well.  If it failed to do both, then I would switch back to the current dosage.  It doesn't hurt to try, right?

  If the mutation test is not very useful at this level, why would my Onc want to do it.  And he is going to use it to determine which TKI to switch to, if I decide to switch.  Does it make sense?

[Trey]

Increased dosage of Tasigna is reasonable to try.  Your situation does not act like a kinase mutation.  If a person has a TKI resistant  kinase mutation the PCR rises rapidly.  So the test is most useful when the PCR rises rapidly and the person loses CCyR.  Doing the Kinase Mutation Test in your case is not very useful for two reasons, but there is no harm in doing it if the Onc wants to.   

[TeddyB]

Good luck if you decide to go with the increased dosage Ray, lets hope it kicks the pcr down!

[Ray99]

Teddy, Trey

   Thanks, I will keep you posted.

[JoshLee]

Hi,

    I may be able to offer some perspective on this. I started on Tasigna and within 11 months I was CCyR confirmed by BMB. Along with that, my PCR was around 1-4% IS....There it stayed for the better part of two years. I went up to Tasigna 400 mg 2x and it had no effect on my PCR. I decided I wanted a second opinion so I went to Talpaz and he switched me to Sprycel 70 mg to start out with. About a month ago I switched to 100mg and have since begun my first downward trend since I stalled. I actually just got my first reading under 1% ever. I'll be 3 years out in December. I am not MMR yet, but I guess what I am saying is that you are CCyR and I've seen 3 different doctors because I was freaking out so much about not being MMR and who knows if I'll ever get there. If you feel good and your disease is suppressed then you're good to go. If something was wrong, you wouldn't see a little tick from .11 to .17 you would see it rapidly rising. I think we like to think that our disease is peeking around the corner to see if anyone is around when we see these small upticks, but there is so much "noise" in a PCR that nobody can really tell what the deal is.  I once emailed Dr. Druker and he told me that stable is good and that he has a lot of patients who's PCR's are frozen between CCyR and MMR and he considers their response to be equal to MMR. From a fellow control freak and a worry wart....I feel your pain!

[Ray99]

Josh,

     Thank you for sharing your experience.  My Onc has the same opinion that 400mg might not help.  But does not mind if I want to try it.  He also said that as long as the PCR stay near MMR, he does not see any reason to change.  But he also understand my anxiety and willing to do a BMB for mutation test just to make me feel better I guess.  With your and CDW's experience, I feel comfortable to stay the course for now.

Ray