7 replies to this topic

[CallMeLucky]

It seems like lately there have been a flurry of articles about the potential for some CML patients to stop treatment.  We have write ups about some new trials that are underway as well as focused on reducing dosage and possibly stopping treatment.  I found it interesting when I received an email today for CMLEarth today, which is a support network run by Novartis.

"While there are several drugs available to treat Ph+ CML, none of them provide a cure, and they must be taken regularly every day in order to maintain their efficacy. So when a cure isn't your goal, what is? That's an important question to answer, because knowing your goal means understanding what you're getting out of treatment, and why you should stick with it. Fortunately, for Ph+ CML, the goals of treatment are clear.

The two main goals of treatment of Ph+ CML are:

      1.       Reducing the amount of leukemic cells in your body

      2.       Preventing disease progression

By understanding these goals, you'll always know what you're working towards. You'll know why it's important to remember your meds each day, and why you are staying on treatment in the long run. In essence, knowing your goal makes it easier to incorporate your treatment into your everyday life. "

Some subtle and less than subtle messages there.  I'm not saying they are wrong, in fact I think there is some danger in all these articles because there are people who will read them and decide to stop taking their meds on their own.  So not trying to be a pessimist and call out the big bad pharmaceutical company, but if I did want to be cynical you could really see this in a way that makes it seem like they are trying to dissuade you from thinking about cessation.

[scuba]

Money is a powerful motivator. Billions of dollars are at stake. Big Pharma has hit the jackpot with a series of drugs that do not cure, have to be taken every day and have a monopoly (patent protection) so that the fees can be huge. And each year they add to the rolls! What a deal. There is zero incentive for big pharma companies to identify ways for their customers to stop taking their drugs. None. As long as the drugs appear safe - they want patients to keep taking them.

There is, however, incentive for governments with socialized medicine paying the bills to find ways for citizens to stop taking these drugs - hence the cessation trials mostly originating in Europe.

We know that cessation alone does not lead to progression when treatment is re-started after a two log increase in PCR. I believe there is zero evidence that anyone has progressed to advanced disease after having been PCRU and re-started on medication after relapse (from cessation). All re-started patients return to their PCRU status.

To me - it seems quite safe to be under a doctors observation and stop treatment, and observe response (via PCRU testing). Each test period that one is PCRU off medication is a blessing. Should one test period continue for two, three, one year, two years without progression - then is it safe to say one is "cured"? We don't know. Personally - I believe that once a person develops CML, the chance that a new stem cell can translocate the 9 & 22 chromosome and re-start the disease from scratch will always exist. So life long testing will be required. But a life without having to take a TKI but with regular PCR testing will be just fine.

When they discover how to activate the body's normal defense against CML (T-cell?) - a true cure is in the future. But I will accept a functional cure.

[momruns]

scuba,

nicely written

loreta

[Poihths]

I'm no fan of Novartis. I totally agree with what has been said here about the corrupting power of the enormous amounts of money invovled.

However, I would also say that the guidance they gave is precisely what any responsible clinician would give to any patient who is not part of a properly conducted clinical trial. The STIM trial for imatinib cessation has only recently gotten to the point where it's run long enough to deliver really interesting results, and even at that, it doesn't have a large group of participants. Last I saw, the ENESTgoal trial (stopping nilotinib) has not even opened for recruitment. The STOP-ITK2G trial only enrolled 19 people across both TKI's. I think the STOP-ITK2G authors put it very well: "Our study provides a reasonable basis for subsequent prospective clinical trials." I know of no large-scale study on TKI cessation.

I personally think the trial results to date hold out a lot of hope, but if I were a physician (like my brother, my father, my grandfather, and my grandfather's brother) I would not advise a patient to stop TKI therapy on the basis of the results so far.

That being said, if I get a chance to participate in one of these trials, I most assuredly will. I'm watching the ENESTgoal listing on clinicaltrials.gov like a hawk.

[CallMeLucky]

I agree with you completely.  I just thought it was interesting the way they come out on the side of being right, but yet there is still an undertone of self interest.  I can't really say there is fault in that, but one thing that I would be dissapointed to see is if people were reluctant to join a cessation study because of these types of messages they are receiving which put it in their head that they can't stop.  Totally agree people should not stop unless in a trial or at the very least with a qualified doctor who is going to properly monitor.

[scuba]

What is monitoring? CML in the chronic phase is a slow disease. Anyone who qualifies to stop taking a TKI is already at PCRU - has been at PCRU for several years. The moment someone like this stops taking their drug - what happens - worse case? In three months there will be an uptick in their PCRU from undetectable to maybe one or two log increase. In three months time ... in six months they will increase perhaps another one or two logs - maybe - and would probably still be negative FISH. Still - a low level of disease. Plenty of time to get back on the drug and have undetectable status re-achieved.

My point is - one can stop taking the drug (like ChrisC is doing) without having to be in any trial* or under any unusual doctor monitoring. Normal PCR monitoring alone would be sufficient to catch anything happening. I do appreciate the fear this can cause when one stops and months have to tick by not knowing if your CML is arrested or growing again - hence the more frequent testing.

Personally - I would stop taking the drug (assuming I ever reach PCRU) and then have a PCR test at six weeks. If there is no uptick, I would test in another six weeks. If still no uptick, then I would go to 3 month monitoring. If no uptick, then another 3 month monitor test. If still no uptick - I would go six months and stay at six months for as long as there are no upticks. If after 5 years - there has been no uptick while off a TKI - I would consider myself cured, but I would still have regular PCR tests at six months. I would still monitor since whatever caused my CML could cause it again.

* the exception being your contribution to science. Participating in a trial enables the profession to gather data in a scientific way. You become part of the statistics.

[CallMeLucky]

For me I think the concern comes with hearing about the people who were doing well on TKI drug and suddenly relapsed aggressively with a big jump in PCR.  I know it is not common, but it does happen.  So if that can happen to someone who is on treatment, it seems there is potential that if left unchecked the CML could relapse and possibly aggressively.  this is not likely but I get concerned about being too comfortable, this is a malignancy after all.  Cancer has a way of being unpredictable.  So if a simple blood test more frequently provides piece of mind and the let's call it insurance policy and reduces risk by potentially catching a problem early enough to get on top of it, then I think it is worth it.  If we do everything we can to fight this disease and it turns on us, then so be it - nothing we can do about it, we know we gave it our all.  But if this thing were to turn on us and gets us because we became complacent based on a false sense of security, I couldn't look my family in the eye and I would have no one to blame but myself.  Perhaps it is all just a mental argument, but for me I have found living with CML is more than 50% a mental challenge.

[Poihths]

I would say that the problem with encouraging CML patients who achieve complete molecular response to cease treatment and just do monitoring is very simple: many will also stop monitoring, either because they genuinely, though erroneously, think they're cured, or because they consciously or unconsciously go into denial.

Such a person would be at significant risk. Recovery stats for people who relapse aren't good, especially if they relapse severely.

In the context of a clinical trial, you'll get monitored whether you like it or not unless you drop out. In the context of ordinary patient care, if you drop off the radar, in all likelihood nobody's going to check on you until you turn up in an emergency room in blast crisis.