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Some interesting ASH 2014 papers


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#1 TeddyB

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Posted 09 December 2014 - 04:54 AM

398 ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia

https://ash.confex.c...Paper76344.html

 

 

519 Epic: A Phase 3 Trial of Ponatinib Compared with Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CP-CML)

 

https://ash.confex.c...Paper70542.html

 

151 Interim Analysis of a Pan European Stop Tyrosine Kinase Inhibitor Trial in Chronic Myeloid Leukemia : The EURO-SKI  studystetho.gif

https://ash.confex.c...Paper74060.html

 

512 Cooperative Targeting of Bcl-2 Family Proteins By ABT-199 (GDC-0199) and Tyrosine Kinase Inhibitors to Eradicate Blast Crisis CML and CML Stem/Progenitor Cells

https://ash.confex.c...Paper72972.html

 

 

And a few other articles, these arent from ASH, but worth a look:

 

http://www.scienceda...41128111330.htm

 

http://www.businessw...py#.VIbo_XtKY-q

(Now this in theory sounds great, maybe we can see an individual TKI dose adjustment for most effect and least side effects)

 

 

  • ABT-199 in combo with TKI might actually , dare i say it, cure us, and also help treat BC CML. (Lets hope this one works out)

 

  • A new drug ( ABL001) being tested that works on most mutations, including T315 (in combo with Nilotinib)

 

  • Ponatinib seems like a very potent drug (as we already knew, but i dont mind reading about it again), lets hope they can tweak the dosage right in regards to serious side effects.

 

  • One thing that interested me from the EURO-SKI study was this:

 

"

Recurrence of CML, defined as loss of MMR, was observed in 43/92 pts (47%) treated <8 years, as compared to 23/87 pts (26%) treated for >8 years (p= 0.005). So far, there was a trend for prognostic significance of MR4 duration: 33/71 pts with MR4 <5 years  (46%) lost MMR within 6 mo as compared to 28/87 pts (32%) with MR4duration >5 years (p=0.07).

No significant difference was observed for relapse within 6 mo according to depth of molecular response at discontinuation (MR4 vs MR4.5 vs MR5).  "

"TKI cessation was a safe procedure but a substantial proportion of pts reported transitory musculoskeletal pain starting within weeks after imatinib discontinuation. The phenomenon was described in 30% of Swedish patients as a "TKI withdrawal syndrome" (Richter JCO 2014). "

 

 

 

So patients who have been < MR 4 longer than 5-8 years, have a much better chance of not having the CML return, and it doesnt seem to matter if you are MR 4 or PCRU?

Also, "TKI withdrawal syndrome" does not sound particilary fun. Maybe its just the swedes that get it :ph34r:

 

Maybe my thoughts on this are wrong, please correct me if so, it feels pretty exciting to be reading about all this, and it gives me hope of a bright future, to bad i cant understand it all as im a not a Doctor, nor do i have the insights of some of the people on this forum :)

 

PS: The part of about the swedes was of course intended as a bit of a joke, i hope noone gets offended.



#2 Trey

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Posted 09 December 2014 - 09:49 PM

The part about "Recurrence of CML, defined as loss of MMR, was observed in 43/92 pts (47%) treated <8 years, as compared to 23/87 pts (26%) treated for >8 years" is significant for those contemplating stopping drug therapy.  In plain language it says:

It is better to take the drugs 8 years or longer before stopping drug therapy because the success rate is roughly doubled.


Edited by Trey, 09 December 2014 - 09:50 PM.


#3 jmoorhou

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Posted 09 December 2014 - 10:48 PM

I hope I'm not hearing that 8 years is the point at which some...many.. people develop mutations while taking 400 mg Gleevec..because it seems to me my Onc mentioned that is the magic number she can promise..but not guarantee after that...


Diagnosed 3/2014 WBC 28 Non detectable within 3 monthsGleevec 400 mg 5/2014 one hour after dinner really improves nausea300 mg 12/15/2016200 mg and 300 mg Gleevec 2/25/2017 (after 3 years on Gleevec) For last four months taking 300 mg per day. Last CMC showed liver enzymes elevated, went to a good Naturopath and he recommended 4 Tumeric, 10,000 mg Vitamen D, and 3 milk thistle (silymarin) daily. Also use One<p>Day Detox Dandeloin tea, and Nettle Tea and a slice of ginger every day...in two months liver tests were below normal.Janis

#4 SUE

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Posted 09 December 2014 - 10:48 PM

Trey,

 

Would that statistic apply to those who changed to lower dosage over the 8 year period,  or just to people who took the recommended dose for the entire period?

 

Thanks,

Sue


Dx  April 2013, FISH 62,  BMB not enough for PCR test; put on Gleevec 400;

 August 2013, FISH 8.7;

Oct 2013, FISH 5.6

Stopped Gleevec Nov 2013 for 6 weeks due to terrible side effects; Jan 2014 started Sprycel 50mg;

Feb, 2014 PCR  6.8

May,2014  PCR   .149

Aug, 2014 PCR    .015

Nov. 2014 PCRU

March, 2016  went down to 40mg Sprycel

Oct. 2016   stopped Sprycel for a couple weeks due to concern about shortness of breath.  Echo showed mild PAH.

Nov 1 2016  resumed Sprycel 20 mg daily 

Dec 2016  PCRU

March 2017  PCR 0.020

May 2017     PCRU

Sept  2017   PCRU

Dec    2017  PCRU

 


#5 gerry

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Posted 09 December 2014 - 11:10 PM

Interesting that there is still relapse after >8years for some.



#6 TeddyB

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Posted 10 December 2014 - 03:25 AM

Thanks for clearing that up Trey.

Seeing as most of these patients were treated with Imatinib, i wonder if Nilotinib/Dasatinib/Bosutinib/Ponatinib will have simular numbers or maybe these more potent drugs, will be more effective for stopping treatment within a shorter timeframe, who knows :)

 

I hope I'm not hearing that 8 years is the point at which some...many.. people develop mutations while taking 400 mg Gleevec..because it seems to me my Onc mentioned that is the magic number she can promise..but not guarantee after that...

 

No, its telling us that in a clinical trial, around 74% of patients who were on the drug for 8 years or more, and had a deep molecular response for some years, has gone off the TKI completly and the CML is not returning.

 

 

Interesting that there is still relapse after >8years for some.

26% relapse is still 74% success, so not bad at all :)

 

From this study, It would seem that the chance of success increases by each year, much in correlation with what some of the members on this board have said.

 

And from what i have read earlier, people can try again later on if not successful on the first go.



#7 gerry

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Posted 10 December 2014 - 06:54 PM

Hi Teddy,

 

I'm more interested in why it hangs around for some people.

 

It will be interesting to see the results of the UK trial for people that are in MMR and have stopped taking the TKI.

 

One of the other papers seemed to indicate that if you were 2 years treatment free then you wouldn't relapse, but they admitted that more work needed to be done for this. I'm not enitirely sure about that either. At the moment I figure I'm going to be tested the rest of my life.






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