27 replies to this topic

[Buzzm1]

Moving treatment-free remission into mainstream clinical practice in CML http://bit.ly/29BHfOo

 

Abstract

 

The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacologic control is the paradigm. Recent trials demonstrate that some CML patients who have achieved stable deep molecular response can safely cease their therapy without relapsing (treatment free remission [TFR]). Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy. Based on the accumulated data on TFR, we propose that it is now time to change our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity. For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting. We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.

 

Read more: http://www.bloodjour...ked=true#sec-10

 

[kat73]

Thanks, Buzz.  Really helpful and comprehensive.  I had never heard of the DADI study and that would be the most relevant to me.  One thing I wonder about - when they talk about "resistant" to a TKI, do they mean not meeting the optimal level (as in time, like a turtle) or do they mean a failure to reach CCyR or MMR at all?  (I'm asking this in the context of their describing "resistance" as being a possible disqualifier for a trial for TFR - yellow or red box, i.e.)

[Buzzm1]

kat73, in Stop Studies 

 

Select patients with CML may safely discontinue dasatinib http://goo.gl/4r2D6G

Dasatinib Discontinuation trial  (DADI) http://bit.ly/1Sc5e9V November 9, 2015

All 63 patients (42 male, 21 female) had been treated with imatinib before the start of the dasatinib treatments.

Median age, 59.5

from an initial 63 with confirmed deep molecular response for at least 1 year

after 6 months, 31 (49%) treatment free

after 20 months, 30 (47.6%) still treatment free

 

resistance refers to those patients requiring a longer time to reach, or maintain, a deep molecular response.

 

Definition and treatment of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia http://bit.ly/29GJe5z

[Buzzm1]

The reality is, the best that most of us can hope for, is being on a low as possible "maintenance dose" for the rest of our lives, or at least until a cure is found.  For those who have a reasonable chance of achieving TFR, not taking the chance, when the known associated risks in doing so are almost negligible, constitutes an acceptance of status quo. 

[Buzzm1]

Cessation of TKI Treatment in Patients with CML May be Beneficial, Says Expert

 

So, if a patient is treated with imatinib (almost 94% of patients on this trial were on first-line imatinib), we identified a cutoff of about 6 years. If, after 6 years of Imatinib treatment, patients are taken off of therapy, about two-thirds of them can do that successfully and, in our analysis, they did not relapse by the sixth month time point after stopping. That was the primary analysis time point. 

 

Read more at: http://www.targetedo...h.aumHZogT.dpuf

 

that would be me ... 

[kat73]

Wow, Buzz, if this pans out longterm, what terrific news.  But what was their definition of "relapse" in this study?  Loss of MMR?

[kat73]

OK, just read the study results.  So, relapse is defined as loss of MMR.  Also, at 24 months the success rate is 51%, which is pretty much in line with other stop studies.  Still, this one is good because of the great number and variety of participants and the criterion of only MR4 to join.  (Yeah, I know, "only" - I wish!)

[Buzzm1]

Wow, Buzz, if this pans out longterm, what terrific news.  But what was their definition of "relapse" in this study?  Loss of MMR?

Yes kat73, relapse in the Euro-SKI study, Part 3, was loss of MMR ... found this note in http://wb.md/28Ai4UM which is part of Stop Studies

 

In terms of duration of treatment, the rate of molecular relapse-free survival at 6 months was 65.5% in patients treated with imatinib for at least 5.8 years and 42.6% for those treated with the drug for 5.8 years or less.

 

for those taking higher efficacy second-line TKIs, the duration of treatment to generate similar statistics could prove to be substantially less

[kat73]

Just gotta get to MR4 and stay there for a couple of years and then . . . I'm outta here!  Hope it happens.

[DebDoodah22]

http://www.ncbi.nlm....pubmed/27488943

Here is the long url for the nih DADI publication.

[Trey]

The 6 year STIM1 trial update on cessation was just released.

 

100 CML patients who had a sustained PCRU (UMRD) for at least 2 years started the STIM study.  Only 16 maintained continuous PCRU all six years.  Another 23 never lost MMR but lost PCRU.  So 39 remained treatment free for all six years. 

 

Depending on how you view the stats, you could either say:

1) 39% succeeded if you count not losing MMR as the metric for success

2) 16% succeeded if you count continuous PCRU as the metric for success

 

http://www.cancernet...on-remains-safe

[gerry]

I am aware of a TFRer having to now return to a TKI after 3 years of cessation. They had blips all the way through, but have now lost MMR. They don't regret being off the TKI for those 3 years and are looking to stop again if/when they reach the appropriate point. :-)

[Buzzm1]

The 6 year STIM1 trial update on cessation was just released.

 

100 CML patients who had a sustained PCRU (UMRD) for at least 2 years started the STIM study.  Only 16 maintained continuous PCRU all six years.  Another 23 never lost MMR but lost PCRU.  So 39 remained treatment free for all six years. 

 

Depending on how you view the stats, you could either say:

1) 39% succeeded if you count not losing MMR as the metric for success

2) 16% succeeded if you count continuous PCRU as the metric for success

 

http://www.cancernet...on-remains-safe

Trey, thanks for the update; added it to Stop Studies

[r06ue1]

The 6 year STIM1 trial update on cessation was just released.

 

100 CML patients who had a sustained PCRU (UMRD) for at least 2 years started the STIM study.  Only 16 maintained continuous PCRU all six years.  Another 23 never lost MMR but lost PCRU.  So 39 remained treatment free for all six years. 

 

Depending on how you view the stats, you could either say:

1) 39% succeeded if you count not losing MMR as the metric for success

2) 16% succeeded if you count continuous PCRU as the metric for success

 

http://www.cancernet...on-remains-safe

 

Yeah, sort of figured this, the longer they go, the more people drop off.  The CML stem cells simply are not dying and our bodies immune systems are not able to target them.  Just need to wait for the trials in the UK and other places with the stem cell targeting therapies and immunotherapy to truly be cured of this disease.

[gerry]

The 6 year STIM1 trial update on cessation was just released.

 

100 CML patients who had a sustained PCRU (UMRD) for at least 2 years started the STIM study.  Only 16 maintained continuous PCRU all six years.  Another 23 never lost MMR but lost PCRU.  So 39 remained treatment free for all six years. 

 

Depending on how you view the stats, you could either say:

1) 39% succeeded if you count not losing MMR as the metric for success

2) 16% succeeded if you count continuous PCRU as the metric for success

 

http://www.cancernet...on-remains-safe

I was a bit slack and only just read this now - still shows for most people that if you can get past the first six months and not lose MMR that you can continue to be treatment free.

[SandyG353]

Hi Everyone.

If my daughter's numbers are still 000 , her oncologist will have her cease taking Gleevec.  She has been in  molecular remission for 7 and a half years.  The doctor was against doing this years ago, but told her if she wanted to be in a trial,  Hackensack Hospital in New Jersey was doing the trial to stop Gleevec.  Her oncologist gave her some kind of test with which he was happy with the results.I believe the test showed that she would not have any resistance to any other drug  used for CML.  This was a precaution to make sure that if she went off Gleevec, that drug or another would put her back in remission if she failed to maintain molecular remission.  He stated that if her numbers are still at 000 in November, he will have her stop the Gleevec and monitor her.  He stated that he has been to many conferences on the topic  and feels that it would be the right thing to do for her.  The only concern we have is that the hospital changed labs and the last test she had showed a slight elevation of the 000.  That could be lab error or due to change in labs.  It didn't concern him.  He will base his decision on the November blood test. .

[r06ue1]

As long as she doesn't lose MMR, she should be fine.  Just make sure they do the testing monthly.  

 

If she does fail the trial, get back to undetected and then try dosage reduction instead, 200 mg should be enough to keep her at zero.

[SandyG353]

I always wondered why her oncologist and Dr. Druker both never felt that my daughter could drop the doseage of Gleevec to 200.  For a period of time she had real bad eyebleeds that lasted for at least a week and came back after a few days.  Dr. Druker had her oncologist do a special test to see how she was absorbing the Gleevec.  Based on the results that showed it to be normal, the two oncologists stated that she should remain on 400.

[gerry]

I have been off Gleevec for 3 years now, still showing negative for blood tests. If your daughter can get through the first six months without losing MMR then there is every chance for her to remain treatment free for a long time. :-)

[gerry]

I always wondered why her oncologist and Dr. Druker both never felt that my daughter could drop the doseage of Gleevec to 200. For a period of time she had real bad eyebleeds that lasted for at least a week and came back after a few days. Dr. Druker had her oncologist do a special test to see how she was absorbing the Gleevec. Based on the results that showed it to be normal, the two oncologists stated that she should remain on 400.

https://www.ncbi.nlm...2/#!po=0.359712
https://www.ncbi.nlm...2/#!po=0.359712
Some articles on tests for levels of TKI in the plasma.