6 replies to this topic

[Johnc]

What is expected on the PCR at 3 months? My onc wants at least a 1 log reduction or he would change my TKI from Gleevec to Spyrel. Is this to high of an expectation to achieve?

Thoughts, Thanks

Johnc

[CallMeLucky]

The NCCN guidelines for treating CML state that at 3 mo, the milestone should be complete hematological response.  You doctor's time line is aggressive.  I would print the guidelines and bring them to next visit, discuss them with him and ask why he wants to diverge from the guidelines.  Ask if there is something high risk about your case that he is looking for a faster response.  In the absence of a good reason to divert from the guidelines (and his desire to beat cancer into the ground is not a good reason) then I would argue it may make sense to give the drug a chance to work before  jumping to another one so quickly.

[tiouki]

The NCCN guidelines are obsolete in a way, recent scientific articles show that the ones with PCR > 10% after 3 months have much higher risk of progression than those with < 10%.

Early response appears to be quite important, and suboptimal response would be a reason to switch to 2nd generation apparently.

http://www.ncbi.nlm....pubmed/22645182

http://www.ncbi.nlm....pubmed/22641468

http://www.ncbi.nlm....pubmed/22683475

Good luck all

Regards

Pierre

[CallMeLucky]

I don't agree that NCCN guidelines are obsolete.  They are updated periodically, I believe every 6 months, and they are based on the collective experience of over 20 CML specialists.

The studies cited are just that, they are studies and they typically represent a small cohort of patients.

Overall I think most would agree that a fast deep response is the best outcome, however I would argue that you introduce additional risk anytime you switch drugs.  If someone is on imatinib and does not have serious side effects it may be wise to give it a chance to work before abandoning it for something that could potentially cause a serious side effect.

The problem with this appraoch is that it makes people who do not get their lightning fast think they are going to have a poor prognosis.  In the academic/statistical sense, maybe that  is the case, but when dealing with real people I think more consideration should go into a drug switch then simply not hitting a certain percentage by X number of weeks.  Especially when basing it on a test like a PCR which has a lot of variability, particularly early on.

I would also caution drawing insights from studies where the methods are not necessarily compatible with what your local lab may be doing.  In the first study, it was based on "BCR-ABL1/ABL1 ratio".  My lab doesn't use ABL1 as the control gene - many don't.  So what does that mean in terms of my ratio to someone else's ratio done at a different lab using a different control gene?  Should I just assume it means the same thing for me?  You could be comparing apples and oranges and not realize it.

I will say that I think the second study is a little more clear in what they are saying, although again the study size was only 45 people.  In this case they are saying at three months your FISH should be less than 10%.  This is at least a more level playing field since the FISH test is much more straight forward.  Still I found it strange they said BCR-ABL positive cells determined by FISH.  My understanding was that FISH has nothing to do with BCR-ABL.  FISH looks for PH+ Chromosome.  Perhaps they are just saying if the FISH detects PH+ then obviously there is BCR-ABL.  Perhaps I am misunderstnaidng something.  Either way I still think this is a small study that suggests what is the highly optimal scenario, but I don't believe this means everyone who is not at this level of response should switch drugs immediately.

Everyone has to do what they think is best for them and if you are not happy with your response and your doctor thinks it is better to switch then by all means switch.  On the other hand I would not let individual studies and over zealous doctors drive us crazy either.  If you are doing well on treatment and your numbers are consistently going down at a good pace and you are meeting the established milestones for today, then that should be good enough, in my opinion.

[Johnc]

Both of your comments are much appreciated and well thought through. I appreciate your time and opions with the info links?

I believe there is no easy answer

Trey

Any thoughts?

Johnc

[Trey]

Unless you show signs that the drug is not working at all there would be no need to switch so early.  -1log is fairly arbitrary, what if it is -.8log?  But having said that, a person does not really need to justify switching to Sprycel or Tasigna.  For many it would be more about the side effects profile, and if Gleevec was working well enough (NCCN Guidelines are the right standard) and the side effects were minimal then you could just stay with it. 

The issue about "faster response is better response" is a chicken and egg issue.  Those who respond quickly do very well, which is obvious because they responded so quickly.  So it is a somewhat circular argument.  But some can respond more quickly to another drug, and they would not know that unless they try it.  But the 12 years of Gleevec history shows that slow and steady also wins the race.

Overall no right or wrong answer unless the drug is clearly not working.

[scuba]

Dr. Cortes told me that slow and steady is just fine - so long as it is steady. Steady down. He cares almost exclusively about Cytogenetics. He wants to see FISH go to zero. It can go to zero slow and steady, but it does need to get to zero for him to feel that liklihood of progression is greatly reduced. Once FISH gets to zero he monitors PCR. And then he only cares if PCR goes back up from whatever baseline residual a patient is at. If PCR goes up for several cycles, he's back to looking at Cytogenetics to see what's going on.

He's had patients with low PCR, but FISH > zero. He is concerned more about them than he is about patients who have higher PCR, but zero FISH.