18 replies to this topic

[CallMeLucky]

http://www.patientpo...eatment-options

[TeddyB]

Very interesting inteview.

According to him, when a patient reaches MMR, chances of progression and mutations are absolutely minimum, anyone know the % who progresses or become resistant after MMR is reached within the current treatment goal of 18 months?

[CallMeLucky]

I don't know the exact but I thought it was less than 1%

[Trey]

The most often used statistic is that if a patient is at least MMR at 2 years the probability of relapse or progression is less than 1% assuming continuation of drug therapy.  The 2 year point (actually about 2.2 years) is important because if any BCR-ABL mutations are going to occur, they will almost always occur within 2 years of diagnosis.  The reason is suspected to be that kinase mutations are not caused by the drug therapy or other outside factors, but rather the instability which causes kinase mutations is there from the beginning of the disease.  So the 2 year point is an important milestone along with response levels since most susceptibilities to kinase mutations will have passed by that 2 year point.

[TeddyB]

Thank you both.

Would it be correct to assume that most mutations occur during the first year, and after that it becomes less likely, and then again after 2 as you say, almost never?

I still have a way to go, almost 10 months into treatment now, but at least im MMR.

Teddy

[teb]

Trey, can you help me understand my test results. I was diagnosed in may 2011 and I still don't have a handle on what I need to do or what results I looking for. I current oncologist I am very unhappy with. He always makes me feel bad when I go on my 3 month check ups, I really feel he thinks I am lying or making up the side effects of gleevec. I am on 300 mg once a day. I haven't  been Able to tolerate an increase to 400 yet. We never get to review my test results because the back and forth we go on the side effects, well I needed a copy of my lab results for a cardiac appt and I just saw that my oncologist did a BCR-ABL test back in December and never told me or called with the results. Am I suppose to be calling for results or does the oncologist call with results? Well anyway here we go...

BCR-ABL/ABL ratio 0.0027600

International Scale:0.077 percent

Interpretation:

The specimen analyzed contains the BCR-ABL MBR translocation (p210) associated with CML. Clinical correlation is recommended.

Comment: RNA was extracted and reverse transcriber toDNA with subsequent amplification and detection by real time PCT using the BCR-ABL  quantification kit from Ipsogen. The ABL gene was amplified as the control. Results are reported as a ratio of BCR-ABL transcripts to ABL transcripts. The limit of detection of this assay is 1 in 100,000 cells. The upper reportable limit for thenInternational Scale is 10%. A value of <0.1% on the International Scale represents a 3 log reduction consistent with the IRIS study.

When I called to ask the dr what the results meant his nurse responded things look good. I asked her about the 3 log reduction she said that always confuses her and she doesn't respond based on that. Can you help me please?

[Trey]

Teddy,

Assuming there are no kinase mutations present at diagnosis, the risks for developing kinase mutations peaks roughly during the 6 - 12 month time-frame post diagnosis, and declines steadily after that.  By the 26th month, assuming MMR, there is about 1% chance of a kinase mutation after that time. 

[CallMeLucky]

My understanding of mutations is that they generally rear up in the first year.  In those cases you tend to see a decline in test results and then at some point they start climbing again which is a sign the smaller mutant population is growing out now that the dominant non-mutant population has been suppressed by the drug.  While there are no guarantees with cancer the incidence of people progressing after reaching MMR is very very small.  The bigger issue for long term patients who have done well is the possibility of developing resistance at some point.  Occasionally you will hear of someone who has been in treatment for years and then suddenly their tests started to go up.  This does not happen often and with the multiple drugs now available I think most of these individuals find that a drug change or increase in dosage works to get them back under control.  Again these are the exceptions with most people who get out of the woods in the first one to two years going on with no issue other than dealing with the side effects of treatment.

[CallMeLucky]

Teb - your results show "International Scale:0.077 percent"

MMR (aka 3 log reduction) on the international scale is 0.1%.  You are below that and therefore in MMR.

Despite your doctor's poor communication skills, you are in fact doing well.

[Trey]

Teb,

Your Onc has not kept you informed about your response to drug therapy, which is the most important issue.  There is no excuse for that. 

You have achieved Major Molecular Response (MMR), which is equivalent to a 3 log reduction.  International Scale 3 log/MMR is .1%, and you are beyond that with .077%, so better than MMR.  So you have achieved MMR in about 18 months [NOTE: updated typo], and on 300mg Gleevec, which is fantastic.  That means you have a very high chance of long term exceptional response.  And you have no reason to increase your dosage. 

The paragraph you copied which starts "The specimen analyzed contains...." is just boilerplate verbiage about how the PCR test is done and means nothing regarding your individual test results, so ignore it. 

Glad to hear you are doing so very well on low dosage Gleevec.  That is quite rare and a very good indicator for long term excellent response.  Too bad your Onc did not set your mind at ease with this information previously.  But now you can hopefully relax a lot more.

Message was edited by: Trey Fox

[teb]

Thank you both for responding. I can definitely take a deep breath My diagnosis was may 2011 so I guess I achieved MMR 19 months on 300mg. Now I just have to deal with the side effects. Thank you again for being there for me. I also think its time to look for a new dr.  I switched to this one when my dr inNYC told me commuting to NY was to much on me. Now I've been so down and out with him. But I'm in the middle of applying for LTD and he has also been very difficult thru this process,

[jjg]

Hi Teb,

I read that you've tried both tasigna and now glivec and now having to apply for LTD. Are you applying for LTD because of the gleevec side effects or something else? Is there a reason why you can't try sprycel or the other 2 newly approved TKIs to try and improve your side effects? I'm just wondering because it seems you've had a rough time with both side effects and doctors. I mean if your doctor didn't tell you that you're MMR (0.077% is a 3.1 log reduction) than maybe they haven't provided the option of changing drugs for QoL / side effect reasons.

All the best.

[TeddyB]

Trey and CallMeLucky, thank you again for clearing that up.

Im awaiting my 9 month pcr results now, 6month results were 0.1%(ABL1) and 0.08%(GUS) IS so im hoping for a continued good response on 400mg G, and i feel pretty confident that even IF some kind of mutation or resistance should occur down the road (knock on wood), the second or third gen tki`s will hopefully do the trick.

Teddy

[teb]

Yes I am applying for LTD due to the side effects of gleevec. I was commuting into Manhattan 5 days a week and the 10 hour days and the side effects I have absolutely no quality of life. My dr did mention possibility of switching but I will not be able to afford the new meds as I grow older. I am keeping my fingers crossed that gleevec will eventually go generic. As I mentioned this to my dr he told me I should then look into the free clinic. I don't know how people with CmL work full tme jobs I applaud them. I truly believe that working has taken more of a toll on my life . Trust me I am not looking for an easy way out. I have workers my whole life and at the same company for 25 years. I am 50 with CML and I just want a quality of life.i I have good days ang think I can o this then I have a couple of bad days and realize I can't do this? Does anyone else experience this conflict and are you all working full time jobs or have you applied for disability?

[CallMeLucky]

teb,

I know how you feel, it was hard on Gleevec although I was able to manage it, keep in mind I am about 10 years younger than you so that helps me a bit.  I can tell you that after 2 1/2 years on Gleevec I made the choice to switch.  This was not due to disease, my PCR has been undetectable, I just couldn't deal with the side effects of Gleevec.  I was fatigued all of the time, my head was foggy and I had incredible muscle pain that was progressively getting worse - it was to the point I could barely stand up in the morning.  Since switching to Sprycel it has been a completely new world in living with CML.  Sprycel has its issues that I am working through but very different from Gleevec.  The muscle pain is mostly gone, the fatigue is pretty much gone and my head is clear - I can actually think straight again and people have noticed it who do not know about my illness, just that something is different now.

I get the cost issue and that poses some real challenges.  But something you may want to explore more closely.  Can you not afford to change today or are you anticipating what the costs will be down the road?  Do what you can today to feel as well as you can and figure out the rest as you go (I know easier said that done).  But if you switch and go back to feeling like your old self, the idea of going to work everyday may not bother you anymore.

Best of luck....

[LivingWellWithCML]

Do you guys consider 0.125% IS close enough to be MMR?  Seems like that's where I leveled off around 18 months (did a 6-week retest and it was the identical test result), and my doc isn't willing to test PCR again untl the 2 year milestone.  I constantly wonder if my PCR might be increasing without me knowing it ... since I'm technically still within the first 2 years of treatment.  Still on 400mg Gleevec.

The misery of waiting ............

[jjg]

Hi Teb,

Sorry to hear that cost is a factor. I don't know about the relative costs in the US today (I'm Australian) but as Lucky says there is still a while before Gleevec becomes cheaper and who knows that may cause some serious price competition. I hope that it is possible for you to try another drug for better side effects.

Being able to work full time on TKIs has a lot to do with how lucky you get with side effects. Very little to do with how tough you are. When I was diagnosed I was about as fit and strong as anybody - I ran 100k that week including a light day for my bone marrow biopsy. Work used to be what I did while my body recovered from athletics. Enter gleevec and my sedentary work was suddenly the hardest thing I did; I missed a lot of work, performed really badly and got home more exhausted than I knew was possible. Now that I feel well again (moved to tasigna) I recognize just how bad I was feeling on gleevec - so don't beat yourself up about it - it is real and it is hard.

With gleevec I still exercised - just easy and it always had to right before I took the medication. That helped me feel better but that feeling never carried through much of the day in fact it pretty much got smashed out by the drug. My husband took a video of me after my morning run bouncing around the house, looking very happy and then another video of me 30 mins later about 15mins after taking gleevec and the difference is just so sad. I just mension exercise because I think it really helped me. On gleevec (and later when I had to be on interferon for 3 months - long story) I worked part time. I was officially part time but I did the hours when ever I felt good during the normal full time work day. I normally only have max 10 hours a week when I absolutely have to be at work and I was always able to get these done... sometimes only just. On gleevec sometimes I would delay breakfast & taking the drug til 11 and take it at work so that I could be at my best btw 8-11. Then the next couple of hours I was present at work but not really working. As you can see I have a very accommodating employer - they only care that I get my work done and are happy to work with me on working as much as I can. Even with all that I still crashed a lot on weekends, sleeping most of at least one day which is not great. It took a long time for me to give in and go part time but giving myself extra time to deal with side effects certainly made for a happier more balanced life. Not working would have driven me completely insane.

I totally got my life back when I switched to tasigna, which makes me feel both very lucky and also bad for people who struggle on glivec or any of the other treatments.

All the best...

[Trey]

Dan,

The reality is that the PCR is not as accurate as the .00XX results would imply.  And -3 log is not as magic as it might seem.  Close enough is good enough.  Stable is very good.  As Phil might say: "Each day that passes is another day that has gone by."  That does not mean anything at all, but it was an opportunity to try to get Phil to respond with some silly aphorism.  You are doing well.

[valmaria]

I too have no qualtiy of life. I was dx in Feb 2011. I have been on every tki except for ponotinib. My problem is my body doesn't take well to these meds. Every one had dibilitating side effects. Been on and off Gleevec 3 times now....I am back on it and because my numbers started rising, they had to up the dose to 800 mg of Gleevec. The headaches are enough to knock a horse out. Then there is the rash all over my face and arms. The bone pain and muscle spasms are enough to make one wanna scream til they can't scream anymore.  I wake up with swollen eyelids everyday and I haven't even mentioned the nausea and what feels like a knife in my stomach and I won't even go into the sheer exhaustion.  Course I am on anti-nausea meds, but, since they make you sleepy, Lord knows I can't take them during the day...unless of course I wanna sleep the days away.  So , I feel your pain and God only knows I wish I could tell you it goes away, but in my case, it has not.  On the 25th of this month, I have an appt with a specialist at Johns Hopkins......I would actually welcome someone saying to me.....I think its Bone marrow transplant time.

Val