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what happened to those who did not achieve CMR or PCRU with medication ?


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#1 valiantchong

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Posted 02 February 2011 - 10:12 PM

Hi,tn

Most of the discussion is to achieve CCR or CMR, however I believe there are about 20-30% of people who did not achieve the target whitin 2 years with the TKIs. Their BCR-ABL could runs whitin 1%-35%%, who are in MMR. What is the next step ? BMT is innevitable or wait for any progression ?? Anyone could answer ?? What is the longest survivor on MMR ?



#2 PhilB

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Posted 03 February 2011 - 04:15 AM

Hi VC

I think you may be mixing up your responses. The 1-35% range is normally to do with cytology not molecular response.  If you have between 1 and 35% of cells still Ph+ then you have a major cytological response, but not a complete one.

A lot of people on here do obsess with CMR / PCRU ie getting the levels of BCR ABL down below the limits of detection for the PCR test.  Whilst it's a wonderful thing to achieve, it doesn't have that much significance in terms of likely prognosis.  The more important targets are CCyR (all cells negative on a BMB) and MMR (3 log reduction in BCR ABL levels).  If you achieve MMR then the odds of progression are very small indeed and the thinking is you can basically stay there forever.  If you achieve CCyR and maintain it for a few years then it is felt to be just as good as MMR.

If, on the other hand, you only manage a major / partial CR then it still doesn't mean go direct to transplant.  I know of people who have taken a decade of trying different drugs before finally getting to CCyR.

Phil



#3 valiantchong

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Posted 03 February 2011 - 05:59 AM

HI Phil,

Thanks for the info. One more question does that mean the over 20% of population that do not achieve CCR or CMR, CML will not progress further and they are able to live until old age ? Then why most of the patient with increase of BCR-ABL in PCR the doctor will suggest them to consider transplant eventough they are still MMR ?



#4 PhilB

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Posted 03 February 2011 - 08:57 AM

Hi VC,

I don't recognise that 20% statistic, and I'm not sure which level of response it's meant to relate to - there is a world of difference between CCR (which the great majority achieve) and CMR (which only about 20% ever achieve - although this may be rising with the new drugs / more time).

Unless there were other good reasons such as dx in blast phase or a known refractory mutation, transplant would normally only be considered after failure of multiple TKIs.



#5 Buzzm1

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Posted 03 February 2011 - 12:20 PM

was reading up in some of the abbreviations for a better understanding and came across this article:


http://pharmastrateg...y-is-hope.html/

The future:

There are also several other TKIs in development, including bosutinib (Pfizer) and ponatinib (Ariad). 

Ponatinib is particularly exciting because it inhibits the rare T315I mutation,

which none of the others do and is currently in phase II clinical trials

This is one to watch out for in the future.


For the benefit of yourself and others please add your CML history into your Signature

 

02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive

2012 PCRU, PCRU, PCRU, PCRU

2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17

 

At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  

 

In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  

 

longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.

 

Cumulative Gleevec dosage estimated at 830 grams

 

Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  

 

Trey's CML BlogStopping - The OddsStop Studies - Discussion Forum Cessation Study

Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt


#6 Buzzm1

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Posted 04 February 2011 - 03:17 AM

Ponatinib: The Real Deal for Refractory CML?


http://www.medscape....warticle/733862


Dr. Cortes: Yes. They're very interesting results, and as you said, it's the next generation of these tyrosine kinase inhibitors (TKI). Ponatinib is a third-generation TKI, which has the distinct characteristic, as opposed to the other TKIs, of affecting the mutation -- the T315I -- a mutation that is not very common, but we know it's very resistant. None of the drugs that we have now really works in patients who have these mutations. This drug not only can inhibit cells that have this mutation, but it also appears (from preclinical data, anyway) to prevent the emergence of these or any other mutations.

That preclinical work made a very exciting drug for the clinic, so that is what led to this study.[1] This study is a phase 1 study. All of these patients have failed previous therapy with TKIs. Two thirds of these patients have actually failed at least 3 TKIs; these are patients who have gone through one, then another, and then another drug, and they have not responded. The results with ponatinib are very impressive. At least two thirds of patients achieve a major cytogenetic response, and more than half of the patients actually get a complete cytogenetic response. In patients with the T359 mutation, of which only 9 were in chronic phase, all 9 patients responded. These are really unprecedented responses, considering the kind of patients who were included, so it looks like a real drug.


For the benefit of yourself and others please add your CML history into your Signature

 

02/2010 Gleevec 400mg

2011 Two weakly positives, PCRU, weakly positive

2012 PCRU, PCRU, PCRU, PCRU

2013 PCRU, PCRU, PCRU, weakly positive

2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)

2015 300, 250, 200, 150

2016 100, 50/100, 100, 10/17 TFR

2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000

2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17

 

At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.  

 

In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.  

 

longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation.   GFR and creatinine vastly improved after stopping Gleevec.

 

Cumulative Gleevec dosage estimated at 830 grams

 

Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.  

 

Trey's CML BlogStopping - The OddsStop Studies - Discussion Forum Cessation Study

Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt





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