27 replies to this topic

[valiantchong]

Hi,

Is there any risk of staying off TKIa drugs since Sept?  What is the risk if one stop taking interferon after 2 months ?

If one had RT-PCR detected will one need to go back to TKIs or just leave it and stay on monitoring strategy ?

Do you do PCR on BM or pheriperal blood monthly ?

What is the MRD trggering condition to go back to drugs or other strategy ? If detected, small % will you go back to TKIs or Interferon ?

Do you think the last LSC is needed to be killed in order to go off drug ?

Sorry that I asked so many questions, but I am just too eager to stop the drugs as well... I am afraid being a "drug pot" and afraid one day it will crack....

[cherylannes]

Hi V,

All good questions.  What are the risks of staying off of a TKI?  The risk is relapse.  However, from the European STIM trial we see taht patients who did relapse, and usually did so within the first six months, went back on therapy and regained a very good response, see link below.  This is the same risk for IFN, the risk is relapse.

I am not sure what the triggering mechanism is that would put someone back on a TKI if they test positive.  I think it would have to be if they are not stable.  For instance, there is an Italian lady who participated in one of the STIM trials who relapsed but opted not to go back on TKI, however she has stayed at a steady MMR for the past two years.  Obviously if she were to lose this response the right thing to do would be to go on TKI again.  She is monitored very closely because she is in a trial.  There is also someone in Australia who after one year of no TKI started to become detectable again, but he too has stabilized and they have not restarted the TKI( I can't find the paper that I read this in at the moment, but I will keep looking for it).

It is critically important to be very closely monitored as there are some patients who arbitrarily decide to stop treatment and only go once every three months for their checkup.  I know of one patient who did this and developed such a serious mutation that she underwent a BMT this past summer. 

The ideal situation is to sign up to participate in a trial for stopping TKI's.  There isn't any trial like this at the moment in Canada, so my Doctor is watching me very closely.  I have monthly PCR and FISH done on Peripheral blood.  There is no need to have a BM every month, peripheral blood works just as well, see link below.

Links:

This years STIM report at ASH: http://ash.confex.co.../Paper1890.html

Original trial from France: http://bloodjournal....stract/109/1/58

Report from Australia, interestingly points out that some patients who stopped TKI therapy still test positive for BCR ABL using DNA PCR, yet they have not relapsed....http://www.ncbi.nlm....pubmed/20811403

Regarding Peripheral versus Bone Marrow for measuring BCR ABL: http://www.ncbi.nlm....0?dopt=Abstract

Cheers!

[valiantchong]

Hi,

l

Thank you for the answers. What is the doctor recommendation if detected MRD ? To go back to TKIs straight away after 2 or 3 consecutives detection ? How sure will the MRD stay stabilize ?

Is this a safe condition to consider a functionaly cure with MRD ? Any study this could be consider as a sufficient enough cure ?

[cherylannes]

V,

I believe that all the STIM trials recommend that after 2 consectuve tests of positive transcripts for BCR ABL, then you should re-start TKI.  I believe that within the contxt of a clinical trial the PCR is done very quickly after the initial one that showed BCR ABL detection.  However, the patients always have a choice to not go back on therapy, but I think that is a bit risky.  However there are accounts of a few patients who did not restart TKI and have been followed very closely and have not seen a further rise in the BCR Transcrips, yet...

Nothing is sure, all of this is new territory, we are the experiement.  TKI's have only been on the market for the past ten years and we are a very small patient population.

It will take much larger trials with years of gathered evidence in order to say we can be sure about anything.  In reality we will only know we are cured from CML if we happen to live a long life and die in our sleeps of an age related effect, i.e. our hearts just wanted to stop.  Then and only then will we be able to say that this person never had a recurrence of CML in their lifetime, so they must have been cured....

So, following the results of these small trials is important because once we get five year data, as we have now from the original Mahon trial (2005), we be more confident that we are being prudent, to allow more patients to attempt this.

But then again, with the advent of DNA PCR we should be able to predict better which patients have the best chance to not relapse.

In my own personal opinion, being able to stop TKI's safely without relapse is a better definition of a functional cure, then the definition that says a functional cure means staying on drugs for an indefinite period of time...We need more time and data before saying any of this is certain...

Cheers!

[valiantchong]

Hi,

How DNA-PCR could predict better on any patient that will relapse ? Base on present RT PCR could detect 1 BCR-ABL in 1 million cell or 10 million, the only different is the DNA-PCR is more sensitive. But with 10 million it is as good. Hence I do not see, how it could predict better with higher sensitivity unless DNA-PCR could analyze the structure of the DNA differently, then it could predict better if anyone could relapse. If all the patients that stop TKIs were detected with DNA-PCR, what is the different betwen them, than the defect part per million or 10 million ?

With the present understanding of CML, I think every doctor will use BCR-ABL as a indicator if one is cured, which I think only apply to a very small population with present TKIs....Any detection of the gene means there is a chances of replapse. It may takes decade of years before someone to discover any new treatment or enough data to tell how safe or not living is MRD. I begin to wonder since the present detection is reliable and is the indicator for CML, this will contradict with the report for normal individual was found detection of aberant gene without CML hold truth.... So far the better bet is the former...

[cherylannes]

V,

DNA PCR is more specific because it is done using the patients own DNA, this is also what makes it more costly, and the reason why it is used only within the context of a clinical trial at the moment.  However, there are some diagnostic companies who are trying to find a better way to do this.  It is all interesting, because PCR isn't even standardized yet, and now we are moving on to the next best thing.  But I am happy with the advancement of technology.

In the Australian paper I provided a link to, the last paragraph of the abstract is interesting: http://www.nature.co...eu2010185a.html

"Seven of eight patients who sustained CMR off therapy had BCR-ABL1 DNA detected at least once after stopping imatinib, but none has relapsed (follow-up 12-41 months).BCR-ABL1 DNA levels increased in all of the 10 patients who lost CMR soon after imatinib cessation, whereas serial testing of patients in sustained CMR showed a stable level of BCR-ABL1 DNA. This more sensitive assay forBCR-ABL1 provides evidence that even patients who maintain a CMR after stopping imatinib may harbor residual leukemia. A search for intrinsic or extrinsic (for example, immunological) causes for this drug-free leukemic suppression is now indicated."  So, this means that they will look at how and why these patients who harbor residual leukemia but don't relaspe and it may mean to investigate at the immune level.

I do not think we are that far away for many of us to stop drugs for a few reasons.  1.) there has been a significant improvement of the ability for patients to reach MMR and CMR with the newer agents.  2.) Personalized medicine will help take some of the guess work out of the equation.  Personalized medicine is the new frontier in Cancer, and many diagnostic companies are interested in perfecting it because it will also help in reducing the cost of clinical trials.  3.) Our health care systems can simply not afford to keep all CML patients on drugs indefinetly.  There is a great financial pressure to ensure that we get patients off the drug safely and that they maintain good health.  There is no point in getting patients off of drugs and then having them relapse with a more complex and costly version of CML. 4.) importantly there is now five year and four year data that shows that some patients are mainting a drug free remission.

Underlying all of this is the voice of the patient.  If we do not use our voices enough to stress the urgency of this situation, then that is our fault.  We need to keep a certain amount of pressure on our doctors and researchers to let them know that for the majority of us a lifetime of drug taking for this disease is simply not doable.

So, we must chose to stay positive, stay focused and stay active in educating ourselves about this disease and current research.

Cheers!

[valiantchong]

Hi,

Well, thanks for the updates, would like your personal case of stopping drug to inspire us too... wishes all the best. Hopefully the day will not be too long to come for the rest of us.

From the news and data gather, I feel we are still a long way towards the cure,,,,,, wish it could happened within 10 yrs, but from the ASH report which has all the TKIs in que for trial, the glimpse of cure is still not seen in the horizon...

[valiantchong]

Hi Cherylannes,

Was wondering if you could share your update on your personal stop TKI results since Sept last year... hope u are well.. wishes u all the best