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TKI switching - timing and choice recommendations


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#1 scuba

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Posted 21 April 2015 - 07:13 AM

CML guidelines highlight need for TKI switch timing, choice
By Lynda Williams, Senior medwireNews Reporter
20 April 2015

 

http://www.medwirene...ng,_choice.html

 

"Second-line treatment following first-line toxicity can consist of any alternative TKI. Following resistance to imatinib, patients should switch to another TKI, such as dasatinib, nilotinib, bosutinib or ponatinib. From nilotinib, patients should switch to dasatinib, bosutinib or ponatinib, whereas patients with dasatinib resistance should be given nilotinib, bosutinib or ponatinib."

 

A goal of treatment is to lead to treatment free remission (TFR). TFR is a goal for second line TKI's for patients who achieve rapid and deep molecular remission. 


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"


#2 JPD

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Posted 21 April 2015 - 01:37 PM

So they never switch you "down" to Imatinib?  I always hope that if Tasigna aint doing the trick I can try Gleevac first before going to another second line.  I think my onc said they dont do this because if Tasigna fails, they assume Gleevac wont help.  Truth?


January 15: .53%

April 15:       .78%

July 15:      1.1% - upped dosage to 400mg after this test

Oct 15:       .85%

December 15:  .28%

March 16: .29%

July 16: .34%

October 16: .11%

January 17: .081%

April 17: .055%

July 17: .135%

Oct 17: .008%


#3 Lucas

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Posted 21 April 2015 - 01:42 PM

Truth, jpd. In few cases gleevec will work better. Tasigna is around 30 times stronger the gleevec. Probably if you fácil tasigna they will change you to sprycel that binds different áreas. Gleevec and tasigna blind almost the same signals of the bcr-abl. I fail gleevec and i AM doing good on tasigna, but i miss gleevec só much. It was easier and i had no sire effects at all.

#4 scuba

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Posted 21 April 2015 - 01:42 PM

So they never switch you "down" to Imatinib?  I always hope that if Tasigna aint doing the trick I can try Gleevac first before going to another second line.  I think my onc said they dont do this because if Tasigna fails, they assume Gleevac wont help.  Truth?

 

Gleevec and Tasigna are similar drugs structurally. The significant difference is that Tasigna's chemistry fits the bcr-abl ATP pocket more precisely which prevents bcr-abl from getting energy. It stops and dies. Essentially Tasigna fits better than Gleevec for the same spot. If a bcr-abl clone develops such that Tasigna does not fit - it's very likely Gleevec won't fit either. Lock and key is how Tyrosine Kinase Inhibitors work. The key (TKI) must fit the lock (bcr-abl ATP pocket).


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 snowbear

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Posted 21 April 2015 - 03:25 PM

What if  you're on Gleevec and never switched to another TKI ?   Can you still try to stop after a few years or do you have to switch to a stronger TKI first?

 

I'm a long way off from even thinking about stopping, but it is a nice thought.



#6 scuba

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Posted 21 April 2015 - 04:14 PM

What if  you're on Gleevec and never switched to another TKI ?   Can you still try to stop after a few years or do you have to switch to a stronger TKI first?

 

I'm a long way off from even thinking about stopping, but it is a nice thought.

 

Gleevec is the standard for stopping:

http://www.ncbi.nlm....pubmed/20965785

 

This is known as the STIM trial (called ST=stop IM= Imatinib) Imatinib = Gleevec.

The current data on cessation comes form patients who are in CMR for over two years stopping Gleevec. 40% (which is huge in my book) of those who stopped - have not relapsed. They remain undetected. 20% became detected, but stable MMR and the rest showed marked relapse with PCR climbing. Those who relapsed became undetected again after resuming Gleevec. There has been "zero" progression of patients who stopped and then had to resume. 

 

There is emerging data on the other TKI's after cessation, but it's early. 


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"





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