Wanted to record/share my journey to stop taking Gleevec. After reading about the testing and trials conducted in France and the UK to see about stopping therapy i'm going to give it a try. Since Feb. '07 I have been undetectable without a change. My Onc emailed Dr. Druker and got his permission to try, provided that we send another PCR test to a secondary lab for verification of my status. Afterwards, I will start a therapy-free life. My next PCR test will be in Feb. 2012 which brings me out to a full five years. Dr. Druker doesn't recommend this any sooner than two years of consistant PCR undetectable. Wish me luck and any input is welcome.
Yes, we are awaiting recommendations for increased PCR testing from Dr. Drucker. If we don't hear from him then we'll go with every three months for about a year then maybe increase the time beyond that.
Unfortunately, I don't have conclusive data guiding my decision. I don't intend on supplementing my diet any further than I already have. I use turmeric and apple cider vinegar in my food but don't wish to skew the test results if I don't maintain it.
you mentioned Dr Druker does not recommend STIM trial less than 2 years' time of PCRU. Wondering if you have data on the correlation between PCRU time before trial vs STIM success rate duration ?
Personaly I think it is related to personal immune system able to handle any reoccurance, I hope there is a way to strengten our immune system before starting STIM to ensure success rate..
Best of luck, i hope you will continue to post as you get your PCR tests. I will be looking forward to see how your status is holding up over the next 1-2 years. I think you have a good shot if you have been PCRu for 5 years. To me that seems like a solid amount of time. I hope this works for you. Enjoy the time off from treatment.
Joel - All the best to you on this journey. I very much intend to join you assuming I can get to PCRu myself and can stay at that level for one year. My plan is to rely on Curcumin to see if it can keep me PCRu. Not a cure, just a maintenance mechanism that may work for years before I have to resume. If it doesn't work and a subsequent PCR test shows detectable, I'll just go back on therapy and then do what you are doing - and stay on it for 5 years - then try again. And try again and again and again.
Please keep us posted on your follow-up tests.
You said your intention if to go off TKI in one year, however base on present recommendation on STIM data is to be PCRU for at least 2 yr before stopping. Dont you think 1 yr is too soon to even try eventhough u wana try Ayurvedic Curcumnoid 8 g daily. Was wondering did you discuss with your doc on your intention, and what he had to say.
Thank you for everyone's support! I'm definitely looking forward to feeling 100% again :) Not to diminish what the drug has done for me or to seem ungrateful. I know this study is in the back of everyone's minds since it came up so I will be sure to catalog my results as soon as I get them.
I have been undetectable for 2 years now on Sprycel and am thinking about doing the same thing. Did your Onc go for it with some good conversation? I have suggested this to mine and he says no way. The Sprycel does wonders for my counts but I have no quality of life anymore.
I wish you, and everyone feeling to give it a good try, all success! And offer all support to those who shudder to even think of doing it: steady on and good health!
I'm looking to stop Sprycel after two years of PCRU.
It happens that I had a consultation at Stanford a couple of weeks ago specifically to request permission to stop Sprycel, after my onc/hem felt that it was necessary to have back-up on such a decision. I'd begun my presentation to him a year ago in preparation for this move.
I knew to bring to the consultation my history of test results, and any relevant studies, and to carry along inside me all that I've learned here on this board. I strained my brain for a few days prior to the consultation to bring only what was clear and simple as my presentation.
It worked. I'm approved to stop next week, the second anniversary of testing PCRU. There are no local studies to become part of, so it's just me giving it a go, with monthly bw and fingers crossed.
They (MD, Ph.D assistant and the specialist) asked everything, challenged everything, and with what I presented and all the answers I had and the good test results, in the end were happy for me to give it a try, as my test results have been 0.000, a more than 5-log reduction, never any returned trace of CML, since four months after starting Sprycel. Can't ask for a better chance at success.
Yes, I do count my blessings everyday and thank God repeatedly.
Last pills: Sept. 13
I can understand and support Joel's decision to stop TKI therapy after 4+ years PCR undetectable. This is not for everyone. I think there needs to be 2 factors involved to think about this option. One is certainly a long term PCRU -- I would say the longer the better, and 2 years would be a minimum number. The other necessary component would be fast response to TKI therapy. Fast response shows high susceptibility of those higher level leukemic cells to TKI drugs. If this approach is going to work, the high level leukemic cells must be killed off. For it to work over the long term, all leukemic cells must be killed off. The big question remains to be answered: after several years of TKI therapy and PCRU, are the leukemic stem cells all gone? There is no answer to that. Research tells us that they are probably not all gone. But maybe they are. I have suggested (maybe wishful thinking?) that after many years of pounding by TKI drugs, the last leukemic cells would give up because of unknown mechanisms at work.
There is also another less drastic option to reduce TKI dosage which I have previously discussed. I have been PCRU for over 5 years. I reached PCRU in well under a year. I chose Gleevec dosage reduction down to 200mg per day, which I have been doing for 2 years now without loss of PCRU status. I also have almost no side effects.
Joel is doing this in a smart way, under increased monitoring. Anyone who considers this should use the same approach.
Trey, I have been PCRU for 2 years solid now and am only taking 50 mg of Sprycel a day. My issue isn't the Leukemia, it's the side effects. Sprycel is much better on me than Gleevec was, but my quality of life is non existant. I am working less than 20 hrs a week and can barely do that. My Onc's only retort to any of this is let's change medicine. I went off Sprycel for 2 months over this last year and am still PCRU. I would certainly like to see what my alternatives are.
Thanks for letting me gripe,
This is an excellent discussion. Dealing with the side effects is the primary reason I want to stop my TKI. Five naps a day, hearing loss (I hope it is reversable: as Trey has pointed out elsewhere it might be due to edema), brain fog, etc.: gotta deal with these things to improve quality of life. At Stanford, the initial response to my ceasing Sprycel was that since it was working perfectly, why stop? Working perfectly except for the side effects, I responded. And so the discussion was on.
I asked whether reduced dosage might be an option, rather than stopping Sprycel, or in the event that I needed to restart it, might I do so with a lower dosage. Their policy has been and continues to be to only take the full dosage. Their reasoning was that a) most of the TKI is immediately excreted and very little is left in the body to do its work, and b) mutations, particularly the T315i, are the enemy and as there are no open T315i studies right now (he said), if after stopping Sprycel I developed that mutation, there would be no TKI to help me. I responded that I expected that since the Ponatinib trial was going so well, it would be approved by the time I needed it. (SO helpful to bring in what gets discussed here.)
I am hoping that at CML conferences this year there will be good reports on reducing dosage of TKIs after maintaining PCRU over time, to deal with side effects, as it appears that other doctors are working with that option. I'll have to try getting a consultation at USC if CML returns, rather than Stanford, if I want approval for a lower dosage. Each approach is a reasoned approach, yet they differ, and we need to see what results are found with each one.
Hmm, that's interesting what you said, Chris, about their assertion that most of the TKI is excreted immediately. I'd believe that if the drug was simply processed by the kidneys, but I thought that's why the liver is such a concern, because the liver processes the TKI, and I'd assume that would take a while.
I think the issue with reduced dosage is this idea that you could develop a resistance to the drug if there is only a small amount of the drug in you. Kind of the theory with anti-biotics. The disease could learn to adapt if there is not enough drug in the system to kill it all. Now the question is if this is reality and I don't know if anyone knows. I have heard some say yes and others say no. I sure don't know. So while I like the idea of lowering dosage to reduce side effects, it does concern me as well. I'm inclined to try something like full dose for 2 years PCRu (if lucky enough), then reduce to 300 for 18 months and see if I maintain PCRu. Then at that point evaluate if side effects are good enough or if further reduction would help. If good enough, stay another 18 months and then consider cessation, or potentially go to 200 mg, see if PCRu is held for 18 months. At that point it would be 5 years undetectable while at a reduced dosage. If there is no sign of the disease (send a blood sample to another lab just to see if anything shows up) Then at that point take a chance on stopping. Although I'll tell you , if I am PCRu at reduced dosage with no side effects, and by that time Gleevec is generic, I might be inclined to just stay on it.
I'll add that during dosage reduction or cessation, I would look at supplementing with something like Curcumin of Fever Few.....
seems like a plan. Are you going to remain at your current testing schedule when you try the dosage reduction? I am looking forward to seeing how reducing the dosage could be a possible solution, also, in case my numbers go into the positive after trying to stop therapy completely.
Oh, before the brain fog gets me, I want to endorse the Cascade Cancer Center in Kirkland, WA. Dr. Michele Frank and her nurse Connie watched over me like a hawk with EXCELLENT bedside manner and care! They were so very patient and answered all of my questions when I was at my most frantic and downtrodden. I called for my records since my current Onc. doesn't have the earlier PCR tests on hand and nurse Connie new me right away, five years later! That's remarkable! she was still the same sweet person I remember consoling me in the past. So if any new comers are in that vacinity I HIGHLY recommend you give them a try. They are extremely knowledgable and keep current with the latest information.
so was incorrect when I stated my PCR status. Turns out it was pretty close to undetectable in October 31st at .001. Since my old threads were whisked away in the forum update I will post my early PCR numbers:
2/14/06 (date of diag.): 19.5 (WBC 369K, PLT 1.2M)
Trey, would you be so kind as to share your thoughts on my PCR progress? I have a theory that if I managed to becoming undetectable within that period of time that my chances could be more positive.
You asked me to look at your PCRs and comment. Your PCR story seems to suggest you have as good a chance of success as anyone could hope for since you achieved PCRU in one year. Whether you will find success in this is another thing. I prefer the low dosage route for myself.
Josh, forgive all this discussion if it's not what you were looking for; I am adding what, to me, seems relevant, and am enjoying reading everyone's input.
I've requested that my onc/hem discuss frequency of testing with me (the Stanford specialist left this up to us); I will hear back next week. I have the lab work request for the first month, so I'm set to be tested mid-October (having again been found PCRU in Aug. All tests have always been by Quest's labs). My request to him is, given that reports from the studies all show that relapse happens in the first six month almost exclusively, to have monthly CBCs and PCRs for at least the first six months, then we'll see. Also, as reports are that at least in the beginning, as one's system has to reboot, to begin taking over the work the TKI was doing, in the beginning almost everyone's PCR shows some measure of CML, What is looked for, as we already know from our familiarity with PCRs, is a trend. Reportedly, 50%–70% of folks end up returning to their TKI during the first six months, but it was a continued increase of PCR results that triggered this, not a single, very low reading: often after such a low reading the next result was PCRU in those who have been able to continue w/o a TKI, even over two years later. I suggested to my onc that we'll talk resuming Sprycel if there are results that show more than a 1-log increase twice. Patience is called for, from what I read.
As I see the coming months, it is a matter of doing nothing and accomplishing everything. There will only be results to report here if they happen, or don't happen. I will be quietly recording a personal diary of my supplements, etc., but probably won't be discussing it yet. I will, as always, be following the discussion with relish. Thank you to everyone, and good health to all.
I don't buy the theroy that low dosage TKIs can cause resistance or mutations, just as most good Oncs have also rejected it. Dr Druker has endorsed Gleevec dosage reduction below 400mg after excelent response. Dr Cortes has Michael on steady state 20mg Sprycel. NCCN guidelines discuss low dosage options. The antibiotic analogy is not the same at all -- in fact it is just the opposite. TKI drugs do not partially kill or stun a leukemic cell as low dosage antibiotics can. Leukemic cells cannot come back "stronger" like bacteria can. Leukemia does not spread to others after becoming "stronger"after being stunned. TKIs at first are too low of a dosage to handle all the leukemic cells in the body, so is that called "low dosage" that could cause resistance? No. I have addressed these issues in the following thread:
To clarify, I am not a big subscriber to the resistance as a comparison to antibiotics, I only mentioned it because I have heard that argument thrown around. The argument I find more credible was the one presented my Dr. Mauro when he spoke about the possibility of clonal evolution under reduced dosage. He wasn't saying that would happen, I understood it to be a possible reason to be cautious. His stand was pretty much until there are trials that show it is safe, he is recommending patients stay at the full dose. Now that is also what he said to a room full of people at a conference, I don't know how that correlates to what he does with his patients in a one on one situation.
Clonal evolution (disease progression) can certainly occur when a person has a high leukemic load and takes too little drug to fight the leukemia, generally due to side effects caused by the drug that do not allow the person to tolerate a full dosage. That is an issue of inability to take an adequate dosage to fight the CML.
Good luck, Joel! Please do keep us posted. I think we're all looking forward to see how you do.
I hope to one day be able to reduce my dosage, but I would be wary of stopping--just a personal opinion. I do know that before my 6-month FISH and PCR, my oncologist said he has reduced dosages for his other patients that are on Gleevec (I'm actually on Tasigna) and they maintain PCRU.
At six months, I went from 96.5% FISH and whatever my PCR was (I don't know my dx number) to negative fish and 0.003% PCR. We did a BMB tuesday just to look deeper at everything. I hope since I have responded quickly I will be a candidate in a couple of years to reduce dosage, if I can continue to improve and achieve PCRU.
I think a high initial dosage followed by long term, low-level maintenance may be the future for the majority of people, although some will be able to pull off cutting the medicine completely. It would seem to me that with initial high amounts of leukemia cells, you need all the medicine you can to go around killing the cells; but if there are later only a few stem cells that wake up in a while, you would only need a minute amount in the blood stream to be taken up by the cells when they awaken.
Anyway, just my two cents. I am excited whenever I see posts like this, not in the sense of a cure or getting out of taking TKIs, but just because we may be seeing a welcome change in how therapy is done.
Hi: I will pray that you do very well with stopping your Gleevec. I have been on Gleevec since 2000, and been PCRU for 8 years, and I am sure you see the notes from Michael telling me I am cured. I really love him for all the encouragement he gives me. I am still afraid to do anything like that. My Oncologist did tell me that there will be a test in 5 years time that will show something with regard to staying PCRU, and being considered cured. I am not sure exactly what she was talking about.
Please keep us all informed of your progress. Its people like you who are willing to take the chance to help others like me who are still leary.
God Bless You
OK folks, my first post after lurking around and benefitting from the info on these boards for seven years. I thought it time for me to offer my own experience, advise and well wishes to those who are attempting to get off of TKI's after being PCRU for an extended period. I was dxd 7/25/2004 with 255,000 wbc. While in the hospital I read-up on clinical trials that showed increasing response to dose of Gleevec so I requested and was allowed to start on 800 mg Gleevec/dy. Within 5 mos. I was PCRU (Quest 0.000 pcr), reduced dose to 600 mg/dy after 9 mos, then 400 mg after 12 mos and stayed PCRU the whole time. In the fall of 2008 (4 yrs after dxd) my liver enzymes (AST/ALT) started unexplicably increasing and continued to climb above 5x UNL in January 2009. My onc put me on a Gleevec "vacation" with the goal for my liver enzymes to return to the normal range. The onc measured my liver enzymes monthly, but left me on my quarterly schedule for BCR/ABL pcr analysis. It took three mos. for my liver enzymes to return to normal range (non-drinker, but take 5 mg Crestor). When I did my next BCR/ABL pcr in the beginning of April 2009, the result was above 100% on international scale (Quest, 10.485 pcr). I immediately did a repeat with mutation analysis; pcr was the same 100% range and showed the BP35I insert mutation (search Trey's postings). I got a new onc and requested, and was put on, 100 mg/dy Sprycel, six weeks later (end of May 2009) I was re-tested and was PCRU again - that' right from 100%+ to PCRU in 6 weeks. I have been PCRU ever since with quarterly pcrs. I have had virtually no side affects on Sprycel (minor fatigue, minor skin rash).
In January 2011, I reduced Sprycel to 70 mg and after 6 mos and 2 quarterly PCRUs, reduced to 50 mg/dy Sprycel this pas June 2011, while adding 2400 mg/dy Zyflo (Zileuton, again search Trey's posts - I really have chronic bronchitis and am doing this with both my onc's and GP's knowledge and cooperation). My goal is to find the minimum dose that will maintain my PCRU status. My plan is to reduce dose each 6 mos I achieve 2 PCRUs. Next January, I will reduce to 20 mg/dy, then in June 2012, if I am still PCRU, I will discontinue Sprycel and continue Zyflo. I will then begin once per month pcrs for 3 mos, then bi-monthly for the next six mos, if I am still PCRU at that stage I will stop Zyflo, while continuing bi-monthly pcrs for another year. If at any point I become pcr positive, I will revert to the previous dose. I don't advise this for anyone else.
The risk in discontinuing TKI's is that you may develop a mutation that may not be reverseable - Caveat Emptor applies - Buyer Beware!!! If you are going to do this, do it under strict supervision with frequent pcr testing, it may take 6 mos or more for the ultimate result to manifest in pcr testing.
Best of luck to all, but unless you are willing to be a guinea pig, like me, I suggest you wait for more research results to support this option.
DPASS - In six weeks you went from 100% to PCRU - that's remarkable. I wonder if the 100% was incorrect in the first place? CML is a relatively slow disease to get started. Once PCRU, it's hard to fathom that in just 3 months you would have such a spike in transcripts (or maybe not?) without a corresponding jump in WBC's? and then crash back to zero in six weeks ... or maybe the cells had not had enough time to respond to the transcript signal? I'm just very curious about this.
Your goal of dose modulation to maintain PCRU without extra drug is commendable. I am going to do the same thing - but as Trey pointed out - in my case I am already at such a low "maintenance" dose of Sprycel already. The big advantage of low dose is no side affects. I asked Dr. Cortes if I can increase my dose and he said "no". He has more concern about my myelosuppression. Since I had a 2 log PCR drop in two months after re-starting 20mg. Sprycel, he is very encouraged. Notable is that my CBC after one month is little changed - but not going up to normal either. I am just holding steady in a 'safe' zone below normal (ANC = 1.6; Plt = 105). I am myelosuppressed, but only mildly so on 20mg. Sprycel. He is concerned that if I increase my dose - I'll have major mylosuppression issues again.
I am intrigued with your Zileuton usage. Dr. Li (U Mass) is doing research on Zileuton's affect on CML stem cells. Coupled with a TKI it could produce a "cure" breakthrough. I have personally come to the conclusion, however, that a cure is not possible without T-cell involvment. The recent work with CLL (Dr. June) is very promising in that regard.
DPass - Thank you for passing that information along. It's definitely interesting to hear from someone who's been in a similar boat as me. The possibility that concerns me the most, as with everyone, is developing a mutation or cell evolution (however you want to label it). I'm very curious to know what triggers mutation and if that's possibly one of the tests that was talked about by Susan61's Onc. Not sure how we could help our bodies adjust so that IF there are any abhorent cells left we aren't leaving the door wide open for them to evolve during the washout period. Which, I suppose, is why trials are trying a cocktail of drugs to retrain the body. I suppose it'd be akin to a drug abuser who quits cold turkey and has the dangerous cleansing period because they've replaced their body's natural function with a foreign substance.
At the same time, i'd love to believe in the other idea that this isn't a bacteria or virus and would behave eradically when dosages are messed with. We know soooo much about this illness but still quite a few large hurdles to overcome. I'm a little shocked by DPass not trying to go back to Gleevec, but that must've been a personal decision rather than a Gleevec failed situation. It is interesting that the disease load came back 100% in just three months. Wonder what the WBC counts at that time. That seems more analogous to disease progression at that rate but i'm fairly ignorant to the mechanics of progression.
Still all good information and thank you for sharing it.
ChrisC - I assume you meant Joel (not Josh). This thread is open to anyone that wishes to share my journey and sort of live vicariously. I know this is a risk and there are far more intelligent people here that will be following this so more information is better than too little. share away
My WBC was 5.8k in Jan. 2009 (just before stopping Gleevec), then 35.7k in early April ' 09 before re-start with Sprycel, then 3.8 k at the end of May '09. I have no reason to doubt pcr results as they were all done at Quest. I re-started with Sprycel after consulting with Dr. Druker because of the BP35I insert mutation. While his personal opinion was the BP35I is not kinase active (meaning it is not a location where ATP binds to allow phosphorylation and cell signaling for replication in the presence of kinases - I think I got that right), he thought it to be the more effective TKI in the event it was kinase active or if the BP35I represented the beginning of clonal evolution to a more unstable molecule. Other research (Lee, et al. http://mct.aacrjournals.org/content/7/12/3834.full) indicates the presence of the BP35I mutation may indicate imanitib resistance and clonal evolution. I am not concerned with lowering the dose through time so long as I remain PCRU. Evidently, Sprycel has wiped out the population of 9:22 cells truncated with the BP35I mutation, or at least, they exist below the pcr detection limit for now.
I guess one can't be sure, but the onc's opinion was that it was Gleevec that caused the elevated liver enzymes. In the two years since, while on Sprycel, I have not had a single incidence of above normal range of AST/ALT while my Crestor was increased to 10 mg/dy some time ago. I believe common opinion is that one could return to Gleevec after an episode of increased liver enzymes and brief Gleevec vacation, without further incidence of increased enzymes.
Your response is very different from all others CMLers that I have read. Your response is extremely fast, from 100 to 0 then relapse to > 100 and then 0 again, within less than 3 moths. I was wondering what is your CBC during you stop Gleevec duration. Does your CBC show increase too. ? Since you experienced fast relapse, dont you think it is risky to reduce your dosage ?
I am in major shock. My doctor told me today I could stop taking Gleevec, but it was my decision, I was first Dx 1993 at age 16, had a BMT from a sister, then 11 years later it popped up again in blast phase, another BMT, and I've been on Gleevec 400 and in BCR-ABL remission ever since. ( Forgive my lack of proper terminology.) I feel very fortunate, I do suffer from frequent daily nausea and edema around the eyes, but I've learned to deal with them. I"m scared to do it. Ironically, I"m losing some of my health coverage and my Gleevec bill will be going up to $6000 OOP next year. But to stop Gleevec just because of the expense, at the risk of going through active CML a 3rd time, well, I would appreciate your suggestions and thoughts. Thanks.
I think, you have 2 options now, base from your feedback you would like to continue your medication but on the other hand you are losing your coverage.
If you could afford and dont mind the side effect you will need to pay and continue your medication so it is the current safest choice.
If due to affordability, I think you may wan to consider to reduce your dosage but need to be closely on PCR so that you it will be less burden on the medication and you will have less side effect.
On the ground of stoping medication, you will need to ask the protocol of monitoring with your doctor and if he has already patients doing it safely under his practice. I think one need to be very carefull and if the doctor confident enough to able to detect any progression fast and remedy it before too late.
On what ground he thinks you are safely to discontinue medication and is he an experienced doctor ?