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Novel Assay Could Help Guide Treatment Cessation Decisions in CML


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#1 gerry

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Posted 22 February 2016 - 01:39 AM

A new personalized DNA-based assay can detect very low levels of persistent disease in chronic myeloid leukemia (CML) patients thought to be in deep remission, according to a new study. The test could help with treatment choices regarding cessation of tyrosine kinase inhibitor (TKI) therapy in these patients. A number of recent studies have examined the possibility that some patients could stop TKI therapy after achieving deep molecular remission. "However, the safe introduction of a TKI-withdrawal strategy would require a reliable and cost-effective method for the identification of those patients with the lowest likelihood of relapse," wrote study authors led by Alistair G. Reid, BSc, PhD, of Imperial College London.

http://www.cancernet...n-decisions-cml

#2 scuba

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Posted 22 February 2016 - 09:32 AM

We know already that upwards of 50% of patients who stop therapy after two years PCRU (including some who are MMR) succeed at remaining off their TKI. The remaining 50% relapse within the first 3-6 months (most of them). As CML is a slow disease when in chronic phase - catching the relapse occurs in all cases (I have read of no exception) by monthly PCR testing. This approach is successful and will soon be in the NCCN guidelines. Once a relapsed patients resumes prior therapy they revert to their prior status.

 

The key with DNA-based testing is that it may offer a way for patients with near immediate dramatic achievement of PCRU (within a few months of starting therapy) with an opportunity to try cessation long before two years of PCRU (or even a few months). In this way, many may be successful stopping therapy pretty quickly since their TKI was so effective at dramatic CML reduction. We don't know what subset of patients who exhibit dramatic response would be candidates for this new approach.


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#3 BPilgrim

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Posted 22 February 2016 - 10:59 AM

scuba--

 

You mention that "Once a relapsed patient resumes prior therapy they revert to their prior status."

 

Is there enough long-term data to show that the quick reversion to prior remission status will have the same durability/length as the original remission?

 

In other words...How do we know that stopping and restarting the medication won't change the long-term quality of the regained remission? Or is this not known yet?



#4 scuba

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Posted 22 February 2016 - 11:23 AM

scuba--

 

You mention that "Once a relapsed patient resumes prior therapy they revert to their prior status."

 

Is there enough long-term data to show that the quick reversion to prior remission status will have the same durability/length as the original remission?

 

In other words...How do we know that stopping and restarting the medication won't change the long-term quality of the regained remission? Or is this not know yet?

 

"long-term quality of regained remission" .... ? 

 

by long-term, I assume you mean five years or more. That time period has not occurred yet, but getting close. From a biology perspective I don't think it will make any difference. If a CML clone is not responsive to a TKI is present, it is always present - TKI has no effect. The fact that some clones come and go indicates immune function is occurring. When stopping TKI treatment (in DMR), the clone responsible for disease has a chance to recover its population and re-grow. Resuming therapy simply attacks it again and the studies indicate that the response is swift. 

 

In my own experience stopping and restarting low dose Sprycel, took nine months for my PCR to climb by fits and starts (up some, down, then up a bit more and then down again) by about one log (still below MMR). When I resumed my low dose Sprycel, my PCR dropped back down to where it was (or below since levels below 0.01% are not reported) in only two months. This confirmed in my mind that expansion of CML (in chronic phase) is slowed by the body's attempt to regulate the CML cell growth and the immediate impact of my TKI on that population when therapy resumed. 

 

There is a recent paper suggesting that stopping/starting therapy in a pulsed manner (one month on/one month off) may be as effective in long term treatment. There is also a belief that temporary cessation encourages CML stem cells to enter the G1 cell cycle (reproduce) and that pulsed resumption may in fact deplete the leukemic stem cell pool over time. This last point suggests that on again off again TKI therapy may actually lead to better results long term in ability to eliminate the stem cell pool (note: Leukemic stem cells ARE killed by TKI's, but only when they are dividing. It is because they can remain dormant for long periods of time that stopping therapy leads to relapse because TKI's have no effect on non-dividing cells).

 

http://www.ncbi.nlm....pubmed/24032404


Diagnosed 11 May 2011 (100% FiSH, 155% PCR)

with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein

 

Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate

6-8 grams Curcumin C3 complex.

 

2015 PCR: < 0.01% (M.D. Anderson scale)

2016 PCR: < 0.01% (M.D. Anderson scale) 

March        2017 PCR:     0.01% (M.D. Anderson scale)

June          2017 PCR:     "undetected"

September 2017 PCR:     "undetected"


#5 rcase13

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Posted 22 February 2016 - 01:02 PM

Damn sleeping stem cells! So we need a way to wake them up so we can then whack them on the head.

Exciting to see some progress forward. I wish progress could move faster. They clearly don't realize how impatient I am.

10/01/2014 100% Diagnosis (WBC 278k, Blasts 6%, Spleen extended 20cm)

01/02/2015 0.06% Tasigna 600mg
04/08/2015 0.01% Tasigna 600mg
07/01/2015 0.01% Tasigna 600mg
10/05/2015 0.02% Tasigna 600mg
01/04/2016 0.01% Tasigna 600mg
04/04/2016 PCRU Tasigna 600mg
07/18/2016 PCRU Tasigna 600mg
10/12/2016 PCRU Tasigna 600mg
01/09/2017 PCRU Tasigna 600mg
04/12/2017 PCRU Tasigna 600mg
10/16/2017 PCRU Tasigna 600mg
01/15/2018 PCRU Tasigna 600mg

 

Cancer Sucks!


#6 gerry

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Posted 22 February 2016 - 04:47 PM

Knowing that you can stop will make the decision easier for people. I see more people attempting to stop in my FB group than on open forums. The number relapsing appears similar to trials.




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