18 replies to this topic

[JLS]

It's 5 years since my diagnoses. I achieved CMR fairly quickly and have remained there ever since. I'm extremely grateful for this medication that has saved my life! With that it seems strange that I would even think

of or consider such a trial. I do so only because of my great response so far and the potential for discovery that people can live disease free without continued treatment.

Another factor is the fact that I would love to be free of the side effects that I deal with every day from this medication that negatively impact my and my families quality of life.

I have found a US clinical trial and I am seriously considering taking part. Thoughts?

[mariebow]

That is something to think about, being side effects free and eventually being cured of CML.

[Susan61]

Hi:  I wish you the best if you decide to do the trial.  I did the trial for the Gleevec in 2000, and I am so glad that I did it.  It not only helped me, but so many others when the Gleevec was approved by the FDA.

Keep us all updated on everything.

Susan

[hannibellemo]

From what I understand there is no down side in trying. From what I have read, those who have tried and where unable to remain PCRU were able to regain their former status when resuming their TKI.

You sound as though you have all the qualifications for potential success with the quick attainment of PCRU and keeping it for 5 years!

Good luck!

Pat

Sorry meant to respond to JLS. Hi, Susan!

[scuba]

Hi JLS,

Do It. Do the trial. The good news is that you will be monitored throughout at six week intervals instead of at 12 week intervals. Any change in your PCR status can be caught quickly.

There have been no progression with anyone who stopped taking Gleevec and then resumed when PCR status changed. They all went back into "undetected" (STIM trial data). So your risk is small.

And the cost, I assume, is covered with the more frequent tests (PCR)?

Good luck to you.

Michael

[CallMeLucky]

It is tempting and you should consider, but go in with your eyes open and a realistic expectation that if you stop there is no guarantee if your disease comes back that treatment will control it again.  It most likely will and the small studies that have been done so far seem to show that when the drug was reintroduced remission was achieved again.

No one can guarantee you that you will regain cmr if you stop and start the same way no one can tell you that your cmr is permanent even if you stay on drug.  So my advice is to think it through, weigh the pros and cons and make the decision that works best for you and those that mean the most to you in life.

You should also find out if the trial is going to have your PCR done at a different lab and if it is be sure you get a baseline with the new lab.  I found out that the hospital I used to go to switched to the lab I am using now and a lot of patients, like me, who thought they were pcru are now detectable using the more sensitive assay.

[LLawrence]

Hi, JLS

I hope to be in the situation to participate in a similar trial in 15 mos.  I am stalking that trial.  Based on the review of the studies to date, it looks to me as though I have a less than 50% shot at coming off and staying off my TKI.  I am ok with that if I can be recaptured upon resuming meds.  The ability to experience some time off the meds would (I think) do both my mind and body good.  Good luck, whatever you decide.

LL

[scuba]

Hi Gary,

It's hugely psychological isn't it? I mean one lab has a person at PCRU and it gives peace of mind. Another lab would have that person "detectable" and the mind goes anxious. Two tests on the same blood can be as much as a log apart! What a test.

The reality, in my opinion, is that those who are PCRU probably have millions of cells that are making CML proteins that are too low to be detected, but are there anyway. Some PCRU people may very well be cured and have no CML stem cells left.. The key is can the body keep CML in check once a low status is achieved? or a new disease re-introduces itself (true cure, but re-start of new disease).

Both Susan and Trey have been PCRU for many many years without any detection whatsoever once their initial PCRU was achieved. Do they still have CML? They both continue to take Gleevec on the assumption that they are not "cured" and that if they stop, their PCR may very well go up. But everything I have read and in every discussion I have had with the doctors at M.D. Anderson - CML is the kind of disease that when Blasts are not present, the disease is in a chronic state and reacts to TKI's in the same way as it did before cessation. It is why the cessation studies continue (the current Trial). And that when someone is PCRU for a very long time (greater than 5 years) there is a very good chance the CML is gone. 60% of PCRU cessation patients after two years have had no re-occurrence!

I have read no cases - none- where progression occurred after TKI cessation from a PCRU state. In fact, all cases that did have detection, resumed their PCRU status once the drug was re-introduced. That is quite remarkable. I would be very interested to read/learn if there has been any progression as a result of cessation trials.

I believe this is the reason the researchers are getting more comfortable stopping drug therapy to allow blood counts to normalize rather than keeping the drug going and "stimulating". They did it with me - and allowed me to stay off TKI for 3 months. And then on and off again for many more months until things sorted themselves out.

Of course there is never a 100% guarantee - but 99.99 is pretty good.

At the end of the day, JLS will decide based on comfort level. He (or she?) asked for thoughts. My thought was go for it!

The good news is that CML is very treatable and all of us are going to die of something else.

[GerryL]

Hi JLS,

I'm into my 5th month of stopping Gleevec, retaining CMR so far. I'm due my next blood test next month. When I initially talked with my doc about stopping, he was reluctant, but I'm his first patient to stop and since then he has added another person who is experiencing bad side effects with all three TKIs.

I've found not all side effects have disappeared - were they side effects from the Gleevec not sure now. I still have some fluid retention, but then I'm female and we suffer with it a bit more anyway. I still have some joint issues, but curcumin seems to be helping.

Good luck with what ever you decide to do. I always keep in the back of my mind that if the CML shows up again I'll need to get back on the Gleevec. But as the six month mark gets closer, I grow a bit more sure of things. Following the six months, I'll need to wait another 21 months just to be entirely sure.

I had a friend that had a go at stopping, her CML returned and she went back on the Gleevec. She was only taking 200mg, but has managed to return to PCRU.

[ChrisC]

Hi JLS,

Well done! If you do feel to join the trial, many of us support you. We all have to go by our inner prompt, so that we are comfortable with our decision. I feel that fear is the biggest obstacle to success very often, and we can feel strong and confident when we go with our gut feelings (especially re sharts: run!).

Yesterday I got my latest PCR results: still 0.000 IS, and all blood work entirely in the normal range. Like you, I responded quickly and deeply to [my second] TKIs and was PCRU by 11 months. I received permission to stop taking it when I was PCRU for two years, and that was in Sept. 2011. So I've been off meds for 2 years, 7 months so far, and there has been only 0.000 test results since that first one in Sept. 2009. This is an approved personal trial, as I have no money to travel and participate in a larger trial. For me, it works though.

It felt very right for me to stop, and it has worked out well. I still have fatigue, and to try to address this I brought in the info Trey posted for us a couple of days ago, and others added to, re testing more deeply for thyroid and hormonal causes to side effects from TKIs (my thyroid test was normal, as was everything else for which we tested).

My PCP said that as they had no knowledge of TKIs and their side effects, that I should get my onc to request more testing. My onc said that since I was off TKIs, that my PCP should be the one to request the testing. So, I kept reading to my onc from the studies, and he caved and has referred me to the Endocrinology dept., and they will call me with an appointment soon. There must be a cause for this ongoing fatigue, and while it doesn't mean that when the cause is located that it can be fixed, it still is worth pursuing because maybe I can get back to a more active life!

BTW, there is a closed group on Facebook for folks who have successfully gone off their meds and maintained PCRU for at least six months: maybe see you there someday. We have been asking ourselves questions: who has taken interferon? who has taken hydroxyurea? and so on. So far, we haven't found anything that is common to our being successfully treated with TKIs such that we have then gone on being PCRU when off meds. There are currently 19 members, from around the world, participating in the group — obviously, we all speak English, and there likely are more folks who would join if they spoke English.

Good luck, whatever you decide to do!

ChrisC

[hannibellemo]

I can't believe it's been that long, Chris, since you stopped G! Congratulations, I'm pea green with envy!

Pat

[shelley71]

Hi,

Do you know, have all the cessation trials so far been for Gleevec patients? Does anyone know of trials for Tasigna?

Also, where's the best place to research this? I have found a few published studies online (gleevec trials), but they are all old and I am somehow struggling to research this. Must be the brain fog!

JLS- Go with your instincts! I agree that there seems to be very little risk compared to the benefit of stopping meds, including the benefit to future CML patients. Good luck!

[GerryL]

Hi Shelley,

There is a large trial going on in the UK

DESTINY (DeEscalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in chronic myeloid leukaemia)

http://www.controlle.../ISRCTN74084226

[GerryL]

I'm now starting to think the fluid retention was related to the Gleevec, I had three glasses of wine yesterday and didn't wind up with puffy ankles. I've just started to notice the fluid retention disappearing. Perhaps some side effects take longer to disappear than others.

Hopefully the fatigue will eventually disappear for you Chris.

[Trey]

It is probably low risk, but the percentages are not that impressive for continued long term PCRU after stopping.  My approach is half dosage (200mg per day) after several years of PCRU, not stopping completely.  My personal view is that keeping the CML in the deepest response possible for a long term (maybe something like 10 years???) may result in eventual leukemic stem cell exhaustion, which would be a cure.  This is unproven but is gaining acceptance as a possibility.  If half dosage has minimal side effects as it does for me, then that is a very helpful interim step that has lower risk than stopping.  I am not anti-STOP, just realistic about the percentages and also prefer to focus on the possible TKI cure even if unproven.  But we all have our psychological needs as well, so if TKI drug dependance is a psychological factor, or half dose still has major side effects, then those are issues to consider in the decision making process. 

[shelley71]

Thanks, I'll look it up!

[GerryL]

Hi Trey,

Is there any particular time you might look at stopping, or do you see yourself taking Gleevec indefinitely?

Even if they thought they found a cure, it would still take a number of years to be sure it was a real cure.

[Trey]

I mentioned a round number of 10 years PCRU, but I simply do not know.  High level stem cells can live many years.  But leukemic stem cells may divide more often than normal ones.  And stem cells only get a certain number of divisions before they die, so if they divide faster, they may die faster if they are forced to keep dividing in the face of persistent TKI drug therapy.  That is why I personally have been espousing a leukemic stem cell exhaustion theory since 2009, before it became a published concept among some researchers.   If TKI drugs can exhaust the highest level leukemic stem cells, then it may take something like a decade. 

I like the current clinical trials to test driving leukemic stem cells out of the marrow niche where TKI drugs can kill them.  For now, they hide for years in the marrow niche where drugs cannot penetrate.  That might make a decision to stop completely a possibility for more patients, and sooner than waiting 10 years or so. 

Also, unless much deeper levels of monitoring are developed (down to maybe -6 logs) then there is no way to currently know if stopping is a good idea.  A "barely PCRU" patient should not stop TKI drugs, in my opinion.  But as for now no one knows how "deeply PCRU" they are.

Overall I do not see high risk in stopping for any continuously PCRU patient, but it is the idea of a long term leukemic stem cell exhaustion that I find more interesting to me personally.  But then, my side effects are very manageable.

[GerryL]

Thanks Trey,

The monitoring needs to improve not only for people stopping but for when they think they have come up with a cure, experiments in mice don't always translate into humans. I also watch with interest the new developments as I'd like this disease to not just be treatable, but for everyone to be cured.