11 replies to this topic

[critchhwc]

I had been PCRU for 5 plus years.  Two years ago I began creeping up slowly.  Last February I lost MMR with a 0.2025 and 3 months later to 0.5023. At that time I got a second opinion and that lab returned a result of 0.3200.  I increased Imantinib from 400 mg to 600 mg and had labs run 3 months later from 2 different labs. The lab that previously showed the highest reuslt showed a decrease back to MMR at 0.0425 and the other lab result showed 0.2015; both showing decreases.  The most recent reports have been 0.3255 from the lab that had reported me back in MMR previously, while the other lab was relatively steady at 0.2205. 

 

We requested a mutational analysis and it came back with the following explaination:  unable to perform bcr domain analysis  because bcr b3a2 transcritpt level too low.

 

What the heck am I to make of this? Considering that the test has a margin of error of 1/2 log is it conceiveable that I am still in MMR?  How much of a variance should I allow between labs?  Which should I believe?  I actually talked with the doctor who was the chief pathologist at one of the labs and was told that the margin of error could actually be as high as 1 log.  I am trending upward but how do we establish a threshold that clearly indicates a change in therapy.  All other blood values are normal, cbc, differentials, and hepatic and kidney functions are all good.

 

One of the doctors is ready to switch without ruling out the t315I while the other doctor wants to wait, thinking that if it goes to 1.0 then I should change to dasatinib.  What a tight rope this is to walk.  I feel great and I am a very active 66 year old.

 

Thoughts please.

[hannibellemo]

Critchhwc,

 

This has been brought up before and I will be very interested in reading a reply from those who know way more than I do. I've always heard that checking for mutation when PCR for BCR-ABL was so low was a waste of time and money. The idea that you were PCRU for 5 years and remain low still seems to put a mutation off the table, too. It seems to me if you had a mutation like T315I especially, your BCR-ABL would have gone through the roof in a year's time and you would have lost more than MMR.

 

Perhaps you have developed or are developing a resistance to Gleevec (not unheard of even 5 years out) and need to move to a 2nd generation drug. 

 

At any rate, I will be interested to read what Trey, and others, make of your situation.

 

Good luck!

[critchhwc]

I'm assuming I am in a sort of "gray" area as far as my numbers are concerned. We have to deal with what we have to work with, as far as tests and there limitations are concerned. So, the fact that I am trending upward puts me on alert, but there's a vagueness about it. Maybe a few research dollars can be spent to develop more precise tests.

I am not complaining, our knowledge is much greater than 20 years ago. It's just that a willing soldier needs to know the coordinates of the enemy.

[Trey]

Kinase mutation analysis is only sensitive enough to work above CCyR levels, which is a positive FISH or approx 1% PCR International Scale.  It is indeed a waste of time at your levels. 

 

The other point here is that kinase mutations result in a much more rapid upward trend in PCR.  Your PCR history does not suggest a mutation.  T315i is one of the most rapid PCR risers, so your Onc is off the mark on that.

 

You are using two labs, which is not a bad idea in your situation as you try to figure out your true status.  Is one of them the lab which reported PCRU for 5 years?  Sometimes they change equipment or chemical reagents.  You could ask your Onc to check, but he probably won't.  So you could find out the lab and call them yourself.  You would want to know if they changed something. 

 

We previously discussed your issue and you said you are taking a PPI for GERD.

http://community.lls...mg/#entry159407

The PPIs can interfere with TKI uptake, maybe some of them more than others.  So that could be the problem.  Sometimes (rarely) a gradual loss of response can occur.  But 2nd line TKI drugs usually work well. 

 

Although your situation is stable enough and therefore not a big issue, overall I would switch drugs unless there is a compelling reason to stick with Gleevec.  I realize the new side effects are an unknown issue for switching.  Or you could try another PPI. 

[critchhwc]

Interesting that you bring up the ppi's. It has occurred to me of late to try and wean myself off of omeprazole, I just started tapering off. I am presently down to every other day dosing of the ppi and will go down to every 3 days on Sunday. Perhaps we will discover a correlation. That could be a kind of victory given that I can keep the reflux under control.

Thanks,every explanation should be considered.

[critchhwc]

Trey, I forgot to mention that neither of the two labs that I am using were being used until February of 2014. All of the elevations have occurred since I have returned to my previous retirement residence. In my travels I have used five different labs before returning to Lexington. All other previous labs were consistent in their reports.

[Trey]

It would be helpful to many people to see if stopping the PPI results in lower PCRs.  Please continue to report on this.

[critchhwc]

I most certainly will.  I will be tested again in late February and I will gladly share results.  

[CallMeLucky]

My money is on resistance over mutation. I agree with Pat, if it was T315i you would see steady increase. You could try to ride out a little longer but more than likely you need a new drug. You got 5+ years out of Gleevec which is not bad. Tasigna or Sprycel will likely put you back in MMR and you continue on. It's a marathon.
Best of luck.

[August1]

Hi,

I agree with the others here that a mutution should have pushed your PCR readings a lot higher. Also the fact that you showed improvement by increasing Gleevac seems to point away from mutation as well. 

 

I was originally on Gleevac and switched to Sprycel. I've been a pretty slow responder on both drugs but have also been taking PPIs to control Barrett's esophagus. The PPI has apparently done a great job and my last endoscopy results showed no metaplasia (Barrett's had regressed dramatically) but, my PCR readings have always been a little behind "ideal." I've also tried tapering off of the PPIs but am not sure if it is having any positive effect. I have another PCR test in 3 months and would love to hear your results as well. 

 

Best of luck. It sounds like everything is going to be great for you. 

[rct]

Just throwing it out there, Mrs had some early on troubles, long time ago now, because of thyroid issues.  Just a thought, your story reminded me of it.  They knew little to nothing of thyroid and the associated medications and their interaction with Gleevec uptake, so both thyroid and PCR were messed with for a while to get it straight.  Definitely an effect on uptake, in both directions.

 

Good luck with it.

 

rct

[critchhwc]

Having 9 years of experience with cml and on gleevec the whole time, with newer 2nd and 3rd generation tki's now available I am encouraged. Life and attitude has never been better . I just want to stay informed and try to make informed decisions. Frankly, I place more stock in what we are sharing than I do in the many arrogant doctors who treat you as tho you are are a research number. I am all about quality of life and living with dignity. I like this discussion board because it affords us who are living with CML the opportunity to learn from one another. WE are the key to the figuring this thing out. It is our frontier; our input is invaluable to getting and keeping a leg up on this disease. I listen to you guys, about our idiosyncracies, the various other meds we take that may adversely interact, and all the other details that often the doctors deem insignificant. We can each contribute to the continued improvements of our therapy options.

We can't just sit sit idly by, we need to act on what we share, and most importantly, continue to share our findings with one another.

By the time my next pcr is run I will have been off ppi's for 2 months. I will most certainly post my results, be they good, bad, or indifferent. If I must switch I already know that dasatinib is the drug I will choose to take. That decision will have been made in large part because of what has been shared on this forum, personal experiences, medical journals, pharmokinetics; all that you gave shared.

WE are important to each other. Don't ever forget that! Thanks to each and every one of you.

I'll swim an extra lap for continued success. Stay encouraged!