36 replies to this topic

[Beanie]

Hi Everyone.  My doctor told me at my last visit that they are going to be doing a study later this year at the cancer center I go to.  The study is for people who have been PCRU for two years or more.  The patients are going to stop taking their CML medicine (for me its Gleevec) and see what happens.  He told me that they have done this study in other countries and it shows that approximately 60 percent of people relapse, but once they go back on medication they reach PCRU again.  He said the other 40 percent of the people still don't show any signs of the cancer.  I will (hopefully) be PCRU for two years in June and he told me I could be in this study.  I just wonder how many of you would do it and what your concerns would be by doing it?  I'm sure there is probably a small chance that if you go off the medicine and you relapse that you won't reach PCRU again, and I wonder how many people are willing to chance that.  As you can tell, I don't really know a lot about this except for what my doctor told me and we didn't talk about it for long at all because he said the study hasn't started yet.

[AlejandrosMommy]

This is totally different from what my son has, but being there a 60% chance of relapse... Even if it was only 1%  theres still that chance... You have gone through enough...

[Susan61]

Hi Beanie:  You are probably not familiar with me, but I have had CML since 1998.  Without going into all the details of my journey with CML.  I achieved my PCRU in 2003, and have maintained it all this time on Gleevec 400 mg. since Oct. of 2000.  I have had people tell me to cut back on dose or stop to see what happens.  My Oncologist mentioned a test that will be available in about 5 years where they can tell if you would have a relapse.  I have to ask her again, but nobody else seems to know what she is talking about.  I am so bad with all the medical terms used.

I have constantly said that as long as my Gleevec is not doing anything to the other organs in my body, and just keeping my CML at PCRU then I am not going to take any chances.  There has been no documentation saying that with the TKI that you are cured, and that only a BMT is a chance of being cured. Even a BMT is not 100% positive of a cure, therefore,  I will continue to do what I am doing, and will not rock the boat to try something that might not work.

Susan

[Beanie]

Believe me, Susan, I know who you are.  I have told my mother, and other people who love and worry about me, about you.  It was such a relief to read your posts when I first got diagnosed 2 years ago.  To see that you have been on the exact medicine I am on and have been on it for 12 years and are doing fine, was and is a great relief to me.  I also see that you are one of the first ones to get on here and reassure people that they will be fine when they first get diagnosed and are scared.  So I know who you are and I appreciate all that you do for us on here.  I guess I will have to talk to my doctor a lot more before I decide to do anything.  It just would be so nice to not have to take Gleevec for awhile, and maybe never again.  I'm sick of feeling "weird" all the time, dealing with the stomach issues, and having puffy "frog" eyes!  But that being said, I am not complaining too much because I know it is keeping me alive and I'm thankful that we have the medicine.

[valiantchong]

here is what I think, 1st you will need to understand your risk before making the decision. Yes the doc is right that 60% of people relapsed on that study, and everyone that relapsed had able to regain back their previous condition before stoping TKI. Of coz there will still a small fraction of risk 'what if' ? I think if taking the present medication did not affect your quality of life, may be you should not take the chances to stop TKI. However there is still some people to take the risk due to they do not want to take the medication thru out their life, who knows what is the long term effect of TKIs on us, which is also a risk to our body as it accumulate in us......Well what ever the decision you make I hope you are in the hand of a really good specialist.

You could check out this web site for references : http://www.cmladvoca...adicate&catid=3

You could check out in this board there are a few people trying to stop the medication...however this is just a start, as this is an uncharted water you are ploding....good luck in whatever you do...

[ChrisC]

I'd suggest that you go with you gut: only you know what you feel about risk. Get the latest info, get the facts, feed yourself with what feels right for YOU.

Consider, perhaps, the unknown: what are the facts known about staying on Gleevec for decades/the rest of your life? What is known now is from over 12 years of continuous use, yet are the various side effects all being reported and evaluated properly (we hope so!)?

On the other hand, what is known so far about those ~60% of patients who, after at least two years testing PCRU then stopping Gleevec and losing PCRU within the first six months and restarting Gleevec: they've apparently all regained PCRU right away, without any mutations detected SO FAR. Time will tell. What has been reported so far is very encouraging, and it is great to hear that a proper study is being put together in the U.S.

Dr. Shah mentioned in January 2012 in SF that he had heard that one of the other ~40% who had remained PCRU in the ongoing studies longer than six months has now tested as BCR-ABL detectable, though he didn't say anything more about it. It appears that if you are going to lose PCRU it always happens in the first six months, except for this person, but I've not seen any published information about this person: how long after stopping their TKI did they begin testing positive again? What were the numbers, did they fluctuate over time? How are they doing now? Lots of questions!

There is apparently growing acceptance that for some in these studies who have been PCRU for over two years and then stopped their TKI and then in those first six months been testing detectable just a little, and who then did NOT restart their TKI but continued monthly testing and they remained testing sort of weak positive: testing positive but at steady low numbers, that having low numbers is something to alert to but not be overly concerned about.

Basically, if reading this causes your gut to cringe in fear, being in the study is probably not for you, unless you are a thrill seeker!

As I recently wrote, without being in a study yet with permission and supervision, I have successfully passed the first six month's mark of being off a TKI and still testing 0.000. For me there was no question: this was what I knew was okay for me.

The questions seem to be, if you meet the study's criteria, do you want to add to the growing body of knowledge or not? There are no guarantees in life, so do what suits you: it's not required that you participate if you are afraid to stop your Gleevec.

So that's my $.02, to go with your gut, and if you want to try it out, read up on the published research -- or not, if you trust your onc to do that for you!

ChrisC

[PhilB]

Hi Beanie,

Like most of us, I would love to be in a position to consider it, but for those like yourself who are lucky enough to be PCRU, and have been there for long enough, it could be a tempting proposition.  Logic suggests that there may be some possibility that doing it could adversely impact your long term outcome, but one would also expect that possibility to be incredibly tiny and indeed it has never been observed experimentally with so far everyone who has stopped regaining PCRU quite quickly on resumption of treatment.  I wouldn't be surprised to find that, as long as you are properly monitored, the risks of being killed in an RTA driving back and forth to the cancer centre may be higher than the additional risk of your CML progressing from taking part - but that is just guesswork as there isn't enough data to be completely confident of the safety.

In the end it all comes down to how much the treatrment effects your quality of life.  If you are struggling with the side effects (or with the expense of getting the drug) then I'd bite their hands off to get in the trial.  If you have negligible side effects and easy access to the drugs then you might say why take any risk, however small?  If you are of an age / inclination to have children then this would be the perfect opportunity.

[tiouki]

Hello Beanie,

First of all, congrats for your results, PCRU for almost 2 years this is great

Second, there is a need to clarify what "relapse" means in this context : let's imagine you achieved a 0% PCR in June and start stoping gleevec.

What would happen is that you would be monitored closely each months for 6 months with one PCR test, to see

-if the PCR stays at 0% = you are ok and will probably be gleevec free for the rest of your life

-if the PCR gets positive = you relapsed (BUT in this case you would probably get a very low PCR number, which would still make you be in MMR ( <0.1% PCR). This means 2 things : -1) as PCR is very low you are not in danger at all -2) you would restart taking gleevec and your leukemia will be back in the dormant state it was before.

What I am trying to say is that trying to stop TKI while you are PCRU is not dangerous at all (in no case it led to a progression of the disease, even though you have to get back to gleevec of course).

Moreover, you get almost 1/2 chance to get rid of gleevec which apparently causes you annoying side effects.

In conclusion I think this is a great opportunity to try.

On a personal note, I have been diagnosed 6 months ago, and I really look forward to be at the same place that you are in : to have the chance to try to stop the drug (even though I have no side effects with sprycel).

Let us know how it goes and if you need more details don't hesitate to ask

Pierre

[Beanie]

Wow.... I was really excited about this study when I first heard.  Now I'm not so excited anymore!  Well I guess I will really have to think about it.  I'm sure that since the cancer center I go to is going to be offering it, many of you will be offered this study too.

[Tedsey]

Gotta question.  With all the new(ish) talk about breaks (pulsing) on the drugs to recover counts and dose reduction, what ever happened to the risk of the CML getting worse off the drug or on too low of a dose?  When I was first dx, I had major issues with anemia, low counts, etc.  I still have very low PLT (on Sprycel) 2.5 years later.  My oncs have always been afraid to take me off or reduce my dose for even a minute.  Is it now an established belief that CML does not need a full dose of TKI all the time?  Or is there a decent chance that it could still mutate and get worse when on a holiday (think Phil insinuated this)?  That is still what my onc supports.  So, whaddup?

Teds

P.S.  Beanie, I agree with Chris where you should go with your gut, but Susan makes a very compelling argument in the other direction.  Since the PCR is only sensitive enough to detect BCR-ABL at a certain level (thus, PCRU is not really 0, but undetected by test), I guess until a better test in invented, I would have reservations.  But that is me.  If there is enough support that you go right back to PCRU on the drugs again, that would possibly push me in the other direction.  But, please consider that our drugs are relatively new still.  All the best to you.  Hope you remain PCRU with your next test.

[tiouki]

Hmm, I don't really see what Susan's argument is (no offence).

Scientific tests have shown that for people with PCRU who tried to stop either had no problem but just had to take their gleevec again (= no risk), either were able to spend their life with no medication anymore. To me there is no debate here, just go for it . (under close supervision by your doctors!)

Pierre

[Marnie]

I asked my onc about this (not that I'm in a position to consider going off meds) and I was surprised at his response.  He absolutely does NOT feel that patients should go off of their meds.  My doc is pretty up-to-date and progressive, I think, so I guess I expected him to be excited about all of the research going on with regard to people going off meds.  He was not.  He felt that it was too risky.

Marnie

[PhilB]

Just to clarify what I may, or may not, have been insinuating...

The classic disease model that most doctors are used to is based on things like bacterial infections. In those cases you have little beasties breeding like mad and mutating as they go.  Some are more sensitive to drugs than others.  If you give an insufficient treament with the drugs then it comes back and where it comes back from is the most resistant portion of the disease poulation.  This automatically means that by mucking about with insufficient treatment you are running a big risk of breeding resistance.

CML is different.  The vast majority of the beasties you are zapping are too far down the chain to breed and therefore cannot mutate.  The population in which a lasting mutation could occur is only a tiny proportion of the Ph+ cells in your body.   This leads to a counter argument that all the mutations must be there to begin with and the 'emergence' of a mutation is just because the drugs knock out the plain vanilla CML lines and the mutants come to dominate.

My personal belief is that the real story has to be somewhere between the two.  I entirely buy into the idea that mutations are much more likely to arise in the early, pre-treatment days when there is more reproduction going on in the Ph+ lines.  I remain to be convinced of any mechanism that completely stops mutations in the treatement phase - as opposed to just making them less common - and I am not persuaded there is no truth at all in the idea that the more cells the higher the probablilty of something happening.  I do however believe, and hope I made this clear, that the probabilities involved are very small indeed.

Bottom line, do I believe that if we had a million people PCRU and half tried stopping treatment and half didn't would we get a handful more progressions in the group who stopped?  I think it's possible.  But my feeling is that the risk involved is so small you'd probably need a million people to reliably detect it and therefore it is irrelevant to any one individual.  As I said, I think the risks invoolved in travelling for the additional tests are probably of the same order as the risks of suspending treatment in these studies.

[ChrisC]

Hi Beanie,

It all comes down to what feels right, for the oncs, and for us as patients. The oncs have training that states that this is a chronic situation with no cure, so it's hard to break from that thinking; hospitals have to answer for any deviations from standard practice, though they seem to allow some oncs to go with their gut when prescribing to CML patients, and we await their published reports: this is how the body of knowledge grows for treating CML.

The specialist I consulted with at Stanford in April 2009, and again in August 2011 when he ok'd my personal trial of ceasing Sprycel on the second anniversary of testing 0.000 on Sept. 14, 2011, would not allow any dose reduction at all, saying that the thinking was that we don't yet know if mutations would occur (for which possibility we are so grateful that ponatinib, etc., are just about ready to catch any mutations that MAY appear, however unlikely that is based on research published so far).

I felt that was the hospital policy, very strongly ingrained in him, but by his giving me the go-ahead for my own trial, something he and his assistant both grinned when they said that this was the kind of trial they really loved — someone who fully met the criteria and had an excellent chance of success — I saw how hungry they were for more research to show what these drugs can really do! Zoom zoom, as they say!

We are all different, with and without CML, and the treatments are different at different times by different oncs and using different combinations of medications. Each of us show our own results, and all together we are a picture of CML today.

It is such an exciting time of research and growing knowledge. See today's article Stanford: Antibody offers hope against cancers

http://www.sfgate.co...TL&type=science in which it states: "The Stanford team said the "don't eat me" CD47 signal has long been identified and is associated, in particular, with the treatment of leukemia. CD47 is found in healthy cells but tends to be expressed in higher levels in cancerous cells."

I think it's great news that you have been offered a place in the study, when it starts, and as you say, that likely it will be offered to others. Hooray! From such studies, whatever is learned, we all benefit.

ChrisC

[ChrisC]

As always, very well said, Phil. Thank you.

[Trey]

A couple years ago I developed what I called a "wish-theory" that after taking TKI drugs for years, the originating CML stem cell would give up and die, and TKI drugs might allow us to out-live that  originating CML stem cell.  This has been suggested recently by more serious CML researchers who now call this theory "CML stem cell exhaustion".  Whatever.  So this theory is gaining traction, although still a theory.  But to exhaust the CML stem cells, if it indeed is plausible, would take some time.  Is it 2 years PCRU?  Is it 3 years?  Is it longer?  No one knows.  But at the initial PCRU, the person still has approx 1 million leukemic cells in the body.  At what point does that 1 million become 100K?  How about 100?  How about 1?  How about 0?  No tests can reveal the answers.  I hold to my wish-theory that the longer a person stays on the TKI drugs, the more likely the leukemic stem cells will give up (i.e., exceed their dividing limits) and die off completely.  This is because leukemic cells of all types divide faster than normal stem cells, and since each cell only gets a limited number of divisions, maybe we could out-live the originating CML stem cell by using the TKI drugs even if those drugs did not kill the leukemic stem cells directly.  But if they divide themselves into oblivion, then "ding-dong the witch is dead".  That CML stem cell exhaustion is not at initial PCRU, and probably not at 1 year into PCRU, and maybe not at 2 years into PCRU.  So the point is not necessarily whether PCRU can be re-gained after stoppage and subsequent loss, but rather how short of complete CML eradication did the person stop, and would another year or so have yielded complete eradication?  That is why I favour the reduced TKI dosage rather than stopping drug therapy.  I have been on reduced Gleevec (200mg) for about 3 years now after approx 3 years PCRU.  For me, that is what I am comfortable with.  If I had stopped TKI drugs, I believe I would have allowed the CML go above the 1 million mark again (loss of PCRU), and to me that is dancing with the snake (Texan term).  I don't like snakes.  Ding-dong.  Toast-city, aboral bucko.  FOAD.  Did I digress just then?  So sorry.

So what is the goal of stopping therapy at 2 years PCRU?  If reduced side effects, then why not reduced dosage?  If to see if you are cured, then you will not know anyhow.  If just to stop all drugs, then whatever suits the individual's needs.  There is not one simple answer.  Just each one seeking his own accommodations with the snake.  Shall we dance?

[ChrisC]

Another report from someone who just posted their results of personal stop-TKI trial, after almost 3 years off TKI:

News from Basil in South Africa

http://www.cmlsupport.org.uk/node/7319

For those who are interested in my progress, here goes.

I was on Gleevec 400mg per day until end April 2009. Due to a few rough side effects, and based on a minimum of 4 log reduction over a 2 year period I decided to follow the path of the STIM trials and stop Imatinib.

Well the good news is that I am now 1 month away from 3 years off all treatment.

My last QRT-PCR test done on 19/3/2012. The result: "undetected" (BCR/ABL 0.00011%)

Over this period of 11 tests, I had 5 detected results and 6 undetected results.

The last 4 over a period of 12 months were "Undetected"

My lowest BCR/ABL % result was my last test.

I am now on 4 month intervals between tests and feeling extremely confident about the future.

BTW. I am 67 years old and was diagnosed in July 2003.

Unfortunately there are no official trials like STIM in South Africa so valuable data is being lost. There should be an International Data Bank which could store this valuable information and be used to determine how and why certain patients can achieve these results and others not.

I hope that one day all can achieve this type of response.

Kind wishes to all
Basil

[scuba]

Chris - Just to clarify your note above on a South African man who went off TKI on his own. He reported five detected and six undetected during this time - correct.

Now this is important.

As I read this, he did not stay 'undetected' throughout. Some tests were positive, some were negative and he continued to stay off his treatment.

To me this suggests, he either has residual disease that is being kept under control naturally. Or that bcr-abl is not necessarily the only disease indicator. Just because bcr-abl is present does not necessarily mean disease onset?

I have written in this forum that I believe many people in the general populuation probably have bcr-abl transcripts and are healthy, never to get CML. Dr. Cortes' staff at M.D. Anderson told me that as the PCR test gets more sensitive, they expect many more false positives for disease. They actually worry about that potential problem on the horizon. Now what does that mean? Maybe PCR alone is not sufficient to truly indicate disease progression unless it continually rises. Why would it ever go down on its own unless the body is able to manage it as apparently is happening to Basil (South Africa)?

Transcription errors in DNA is COMMON including the dreaded 9;22 translocation. What causes disease is that the body loses the ability to correct it and it gets out of control.

I have not read any study where (Stim or otherwise) they continued to test patients even after they were positive for bcr-abl. As far as I have read, all patients that became detected went back on their medication. Maybe...I'm just sayin' - they did not need to. They just needed to continue monitoring to see if a trend upward developed. I wonder how many of the 60% could have continued off TKI and still have low levels of PCR even bouncing in and out of PCRu.

I don't fear snakes. I like to dance. I only wish I could sing too.

[Trey]

PCR positive then "positive but reported as not positive".  PCRs are not all that accurate, so this person likely has nearly a million leukemic cells floating around on a regular basis, being maintained by a small number of mid-level leukemic progenitor cells, not by the high level leukemic stem cells (which are presumably still in hiding (quiescence or hibernation).  His body has not eradicated them, so it is not the answer that his body has learned to destroy the CML  A good description of dancing with the snake.  CML is a patient disease.  It can wait for many years before the hibernating leukemic stem cell (or cells) come out of hiding.  Overall the person will likely do fine this way for a while and re-start TKI drugs at some point.  Maybe that is the definition of success for some people, and that is fine.  But what if this person had stayed on the TKI drugs for years longer and became actually cured as a result (although still only a wish-theory)?  Which outcome is better?