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30 month MMR Therapy Goal?


I thought I'd see what people's thoughts are on this paper I recently read:

"Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV"

It seems to conclude that if you have not achieved MMR by 30 months, but still remain under 1%, than your overall outcome is not as good as MMR? Suggesting at 30 months if you are between MMR and CCYR you should switch medications. This seems to disagree with the recent NCCN guidelines and opinons I have received from a CML specialist. I am currently at approximately 30 months and between MMR and CCYR so this is a very relevant topic for me as I consider pushing my oncologist harder to switch medications from Sprycel. I don't understand how the hazard ratio is calculated in this paper, which seems to be the parameter used for this conclusion. I also don't understand whether the differences in hazard ratio are significant between reaching MMR and CCYR at 30 months. I'm hoping someone can shed some light on this topic. Thank you.   

Browsed it briefly but I gleaned the following:

In the "Learning Set" the MMR was always increasing and the number of at risk patients seems to have gone from 534 to 528 so does this mean that only 6 patients either dropped out or progressed?  If I understood that right then I would say this is not telling us very much (other than number of those with MMR is always increasing ;-)

Also in the conclusion it is stating that the later you reach MMR the less likely you are to reach MR4,5.  I think we pretty much already knew that.  I gave up on thinking I would stop taking TKI barring a miracle.  I just want to live my life and lower dosage every chance I get.  

This article was nothing to worry about in my opinion.  I don't think it is saying CCyR = Progression but rather the later you reach MMR the less likely you are to reach MR4,5.  Again read through it quickly but I think that is what it is saying.  

Yeah I wouldn’t read too much into it. Like you I am approaching that 30 month or 2.5 years of no MMR albeit right on the line like yourself and Coloradoguy was. 

If CCYR offers the same overall survival as MMR then why do we worry. It’s because we want to get to that mental point of “I am safe”. None of us have a guarantee MMR or not but we’ve gotta learn to live with the moment and at the moment we are safe if nothing else.

Like Coloradoguy says most do eventually reach MMR as that article implies but it may take much longer for some, I am now of the opinion it’ll happen when it happens. What I have been told is they have to be careful when to switch so as not to introduce mutations. I am still waiting for my analysis to come back it’s been over 4 months now. Most are of the opinion I didn’t need the analysis as I was right on line 0.118 at that point with a small “increase” to 0.164 but who knows. Have to see what that yields, hopefully nothing but at least it’ll inform next steps. I’ll either increase dose or switch. Both prospects are scary but what can we do but ride surf these waves for now.

I do understand your anxiety and I have seen some people who didn’t get even close to MMR until 5-10 years of treatment. So many variables it’s difficult to understand why not but here we are.

”Until about 1.5 years, the MR2 and the MMR curve are almost identical. This corresponds to the clinical experience that for this time period, an MR2 is sufficient in respect for PFS.” So they agree also that CCYR is sufficient. MMR is a cherry and MMR4.5 is the cake.

When do you test again?

alexmcpee and Coloradoguy, thank you for the encouraging words. My concern was with the conclusion of the paper suggesting a medication switch at 30 months if MMR was not reached, but putting it in perspective on progression free survival helps a lot. I actually ended up having my test slightly early, and got my results this past week. The turnaround was incredible. The test was performed at 2 months instead of 3 months on my request. I appreciate that my oncologist was willing to do the test early because of my anxiety with increasing numbers, albeit smaller increases. My most recent test, which comes in at approximately 31 months is 0.199%. It's funny how I feel better with 0.199 versus 0.2. I'll try to relax more and follow your advice. I'm still curious though on the hazard ratio increase at approximately 30 months. I see the definition is the ratio of (risk of outcome in one group)/(risk of outcome in another group), occurring at a given interval of time. Maybe I missed it in my reading, but I don't see how the "risk outcome" is defined. Is reaching MR4 the outcome, is that what you suggested ColoradoGuy? If that's the case of hazard ratio, then I will rest much easier. Thank you to all. This forum is always so helpful.    

I am not sure what it means to switch meds at 30 months. When I switch from Imatinib to eg Dasatinib after 30 months. Do I still have an opportunity to reach DMR ? I cannot conclude that from this article.

Wow that was quick then. Haha yeah mentally those small decreases do effect us although really they’re the same result and that’s fine. I’ve seen various articles that stated that plateaus can last for 1-2 years and hopefully that’s what the case is with us both.

I can’t see how they came to this conclusion in the article I am sure if you’ve been on TKI for 10+ years you’ll continue to drop eventually. Statistics are just that and they’re impersonal at the best of times. I am focusing on staying lower than 1% and anything else is a bonus. But in reality mate we are right on the MMR line and as David Fitz says nothing magical happens in the body at MMR it’s a statistical line in the sand. CML doesn’t care about decimal places of such insignificance. Sure when you have log increases then it matters but even that doesn’t necessarily mean we are advancing. It’s hard I know but hang in there. You’re not alone and I am hanging in there too

Ian, I wouldn't ever recommend that anyone should think of increasing TKI dosage when their CML level is low in an effort to push through to a lower level.  TKIs are toxic medications.  Ollie's onc increased his Imatinib dosage to 600mg 

2015:    0.22    0.16    0.04    0.55    0.42
Moved to Imatinib 600 in 3/2016 (after the PCR reading of 0.71)    
2016:    0.71    0.66    0.13    0.45
2017:    0.18    0.06    0.10    0.07    0.35
2018:    0.04    0.24    0.10    UND   UND (last 6 months were undetectable).

Remembering Ollie (worth reading)

If you switch TKIs your onc will likely insist on starting you on the standard high dosage with the result or side-effects unknown.  Your CML level is already low; you shouldn't require a high TKI dosage to manage it.

Your CML history:
diagnosed February 2nd, 2018 with an enlarged spleen at 25 cm, WBC at 225k, 2% blasts in peripheral blood. started on Sprycel (100 mg).

PCR at diagnosis: 97%
3 months: 3.822%
6 months: 1.069%
9 months: 0.547%
12 months: 0.256%
16 months: 0.315%
19 months: 0.28%
21 months: 0.28%
24 months: 0.106%
27 months: 0.128%
30 months: 0.199%

When CML is rangebound, or plateaued, at a low level for a prolonged period of time, as yours has been, a gradual dosage reduction is typically successful, without it having an adverse effect on your CML level.  Your CML level will move lower with time and it will do so regardless of the dosage you are on at the time, be it 100mg or 20mg.  Think about beginning dosage reduction six weeks prior to your next quarterly test; you could alternate 100mg and 50mg (split), for an average of 75mg, to begin with.  

Here's an example:




My results were: (starting from 3 months) Imatinib 400

26% 2% 0,57% 0,84% 0,74% 

There was a one month time between the values in bold. Other values are every 3 months. 

Imatinib 600

0,35% 0,34% 0,25% 0,17% 0,29% en now they want me to switch to Dasatinib 140mg ...


Hi Buzz, Thank you for the info. I know you have been tracking a lot of different responses and I value your opinion. I would love to lower my dosage and have always had the intent after getting to values below 0.1% for a few consecutive tests. I worry if I do it without reaching smaller values on the order of 0.01% (as shown in your example) I won't be able to maintain my values. Since you have seen a lot of responses, have you seen anyone successfully lower their dose when they were still between 0.1% and 1%? 

Ian, no, you would be the first.  In your situation oncologists typically either increase TKI dosage to exorbitant levels in an effort to push through a low CML level that is presenting no danger to the patient, or switch to a high dosage of another TKI.  At existing low CML levels there is more risk associated with the high TKI dosage than there is with the CML.  Typically CML levels, with time, move lower regardless of the TKI dosage so to me it makes more sense to opt for a continuing lower dosage rather than treat a low CML level with a high, or higher, dosage.  

argearge, I'm not a fan of extremely high TKI dosages.  If you do switch to Sprycel convince your onc to start you on 100mg.

I did not see the "risk outcome" clearly defined either but in the abstract I did gather the following:

"Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later."

Which is in line with what I understood them to be saying, and that is that the longer you go without MMR, the less likely you are for a deep 4, or 5 remission.  I had already assumed this in my own journey so I don't think anything shocking was revealed.  That is what I understood.  It is strange that the slightest lower nuimber will make us feel better but CCyR for months upon months means TKI is doing it's job.  

I did switch to Nilotinib so if you have not switched ever I don't think considering it is a bad idea.  Not necessary but I don't think it could hurt unless you have a bad reaction during which you can always go back to original TKI.

That is precisely what my doctor from the 2nd opinion said. Why 140mg ? You are in chronic phase ...


My doc also wants me to switch to dasatinib from imatinib. However, when I read some papers I am not sure what advantage I can expect from it.

"However, while 2G and 3G TKIs present higher BCR-ABL1 inhibitory activity if compared to IM, they have failed to generate meaningful survival advantages for CML patients. Moreover, it is now apparent that, despite complete inhibition of BCR-ABL1 kinase activity, TKIs are unable to eliminate quiescent Leukemic Stem Cells (LSCs), as these cells are not “oncogene addicted” and therefore require alternative treatment strategies"


I have a bcrabl of 0,29% after 2 years, with 1 year on imatinib 600 instead of 400.

Do it.  Switch to dasatinib.  140 is too much, but it won't do any harm for a couple of months.  By then, I'll lay money you will have a nice reduction in your PCR number and your onc will switch you to 100 or maybe 70.  You'll be fine there for a few months, and then you can show him the literature advocating for 50.  Hopefully at 50 you'll never get a pleural effusion.  But, it's not the end of the world if you do.  I've said this before, and it's not a certainty, but people who respond very very slowly to imatinib seem to see a big lurch downward (and continuing trend downward) with a switch to dasatinib.

Thanks for your answer. The main questions I have is if TFR is still a real goal and can I still play soccer ? I am in a soccer team. I am afraid of the possible adverse effects, especially the cardiovascular ones.

Hi,I changed from400mg  Imatinib when I was at 0.4% to Dasatinib.Doc wanted me to start at 100 mg but I refused so I started on 50 mg .I reached Undetectable in less than five months ,I am now on 40 mg .You should be fine to play soccer ,the side effects of Dasatinib are nothing compared to Imatinib which for me were awful.It seems Dasatinib works differently to Imatinib so there should be some benefit ,Good Luck , Denise.

Thank you. The problem is, I do not have any side effect from the imatinib. What was the reason you changed?