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How important is MMR?

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Hi everyone

I hope you’re all doing well as another year hastens to its end!  Last week I got my one-year PCR test results and I’m a little bit concerned, so I was hoping that someone could advise me.  In brief, my history is as follows:

November 2015: diagnosed with WBC 204 000, enormous spleen (22cm enlarged) and 2% blasts.  I was still in chronic phase, but relatively high risk.  Started on dasatinib.  BCR-Abl: 72%.

I reached the CHR in about 3 weeks and then had three-monthly PCR tests, with these results, all on the international scale:

1.5 months:  36%

3 months: 2.7%

6 months: 1.4%

9 months: 0.57% CCyR

12 months: 0.36% (no MMR but decreasing CCyR).

The ELN guidelines indicate that one should have a MMR after one year, and this hasn’t happened for me.  However, my results indicate a constant drop in BCR-Abl and I know that I was VERY sick when diagnosed – had lost 25kgs and presented with a boatload of symptoms, including night sweats, severe bruising and a very painful spleen.  I am feeling wonderful on dasatinib and have had no side effects at all apart from an eye bleed, a rash and hair that went grey overnight.  Furthermore, there has been no change in my energy levels – I have missed only two days of work since being diagnosed, and that was because of the bone marrow biopsy and associated hospitalisation.  I’d take this situation over a rapid response with terrible side effects any day!

My question is really whether MMR at 12 months is so very important when one has a CCyR, normal blood counts and declining BCR-Abl levels.  My doctor doesn’t think so – she has set me a target of MMR by 18 months and has said that she will change therapy if this goal isn’t reached.  However, I love being able to lead a totally normal life on dasatinib and would hate to change without good reason.  I know that every day spent outside MMR increases the likelihood of losing CCyR and diminishes the probability of ever reaching MMR; however, since I was so very sick when I was diagnosed, I think I’m in a pretty good place and I am sure that I will reach it, perhaps not even by 18 months.  Any thoughts or experiences would be appreciated – I am sure that there are many people out there who didn’t reach the 0.1% level by a year and who are doing great years down the line.

Thank you in advance and all the best for 2017!

Martin

 

 

Hi Martin,

Not all of us respond in the same way, or as quickly as each other. But the most important thing is the trend. Your PCR is going down - perhaps not as quick as the ELNet guidelines would like, but they are just guidelines (thought important ones!). The important thing is that your PCR is dropping and hopefully in the not too distant future you will achieve MMR. 

For what it's worth, it took me almost 2 years to make it to MMR and I'm at around the MR4 point now. Like you, I had some very high counts when diagnosed, a spleen of comparable size and blasts of 10%. Though I don't know the evidence, it stands to reason those of us starting from a "higher" position may take longer to reach MMR.

I think your doctor sounds really sensible about this, and even if you did not hit MMR at 18 months if you still saw a downward trend and were nearly there at that point I would consider sticking to what you are on - as you say, you are tolerating it very well, and that's not the case for everyone and every TKI. If for example you were at 0.15% at 18 months it would seem foolhardy to switch. If you hadn't budged from where you are now, of even gone up, then it would seem sensible to change medication.

But also remember that to see a downward trend, not every result may be lower than the last. My own PCR graph shows an overall downwards trend over the last 4 years, but with plenty of ups and downs in the middle. 

David.

Hi Martin,

I echo what David has already said.... not everyone matches the optimal response times recommended by ELNET. You have had a very good response to dasatinib with decreasing Bcr/Abl levels so I think your doctor is giving you good advice. 18 months to reach MMR or lower is not a bad goal to aim for, but as David says there would be no need to change TKI even at 18 months if your levels continue to drop. I have a CML friend of many years and she took 6 years to get below CCyR - she continues to do well. 

best wishes,

Sandy

Likewise I would  say don’t worry too much, you seem to be in good hands. Your numbers are doing well and falling nicely. You story reads almost as mine, indeed very similar, 95% at diagnosis and 2 days off work, feel great, no side effects on Imatinib though. I fell slowly, 35% at 3 months, just CCyR at 12 ( 1% ) and MMR at 18, just over, I then continued down and indeed tried stopping last year on a trial. I am now at MR4 and all good. Some are slower, the data does show while we are told 0.1 MMR is the place to be a level of 1% and below is still very good long term, I am sure you will get lower. I did consider a change but stuck with my TKI, perhaps if you are so well and numbers falling even if slightly over at 18 month it would be worth sticking with Dasatinib. I am 5 years now, and when first diagnosed and for a year or two after the goals were MMR at 18 months, it is only the past lets say four years this changed to 12 months.

Also, as David said I know some physicians are more interested in the fall, eg 100% at Dx and 30% at 3 months is a threefold drop, the same “arguably” as 30% at Dx and 10% at 3 months. Keep us posted.

Nigel

Dear David, Sandy and Nigel

Thank you so much for replying to my message and for giving me such good advice.  It is really so helpful to hear about your experiences and I’m so glad that you, David and Nigel, are doing so well down the line despite having a drop in PCR levels that wasn’t as fast as is hoped.  Your stories gave me hope for the future and are greatly appreciated, especially as I was hoping for an extra zero before Christmas and didn’t quite get there.  We all want faster and lower, but it really helped me to be reassured by some others who have walked this path that I’m still doing okay.

I think that what is not always clear about CML is how aggressive the disease is in some people.  Most people are diagnosed routinely and almost accidentally, without noticing any symptoms, and at that time I think there is less of a disease burden to get rid of.  Standardising everyone to the international scale and quantifying PCR perhaps doesn’t cater for differences in tumour load at the beginning of therapy – just my view, and not substantiated, but I really believe that I was sicker than most than diagnosed!  Perhaps this is because young(ish) men are notoriously reluctant to go to the doctor – I had to be persuaded by several friends and family members to seek medical attention, and was even misdiagnosed by the first GP I saw. 

I will follow your advice and that of my doctor, which seems very sensible.  I guess it’s like investing on the stock exchange: share prices fluctuate and go up and down regularly, but as long as the overall pattern is upwards, this is suitable.  As my father used to say, “the trend is your friend” on the stock exchange, and I suppose the same applies to BCR-Abl levels.

Thank you all once again, and all the best for the festive season and for the new year.  May all you hope and wish for in 2017 come true!

Martin

Hi everyone

Just an update on my latest results: after 15 months my levels have dropped from 0.36% to a disappointing 0.24%, so it seems unlikely that I will reach MMR by 18 months. The doctor is concerned about possible mutations and has told me that she will do another BMB if I haven't reached the magical 0.1% by June... so there are interesting times ahead for me! It will be a tough decision if I get to 0.15 or 0.16 at the time of the next test as I certainly don't want to switch from dasatinib. Maybe a dose increase will do the trick?

Best wishes from Johannesburg

Martin

Hi Martin,

I understand you're disappointed, but the reduction from 0.36 to 0.24 is a 33% drop. You've wiped a full third off your previous result. Not to be sniffed at!

David.

Hi David

Thank you so much for the reassurance!  I am sure that I will get lower, but I fear I will never truly relax until I reach that 0.1%, which seems so arbitrary yet is so very important.

Best wishes to all on here.

Martin

Hi Martin

If it's any help there is a lot of thinking that anything below 0.5 is 'safe', certainly David Marin has suggested that is the better figure to be more concerned about.

I have had CML for 9 years and have only just started getting numbers of below 0.2 but I am healthy and providing the numbers do not increase then I have learned to accept I may never reach the magical 0.0000 number that we all crave

Karen

Hi Karen,

At CML Horizons last year, two doctors (Steve O'Brien and Giovanni Rosti) both spoke about 1% being a good rule of thumb as a "safe" spot. For example, if they had a patient who hovered around 1% but in a stable manner and all other things being OK then they would not be concerned about that individual.

That said, we all of course want to get our PCRs as low as possible - but the "holy grail" of 0.1% perhaps can be put on a pedestal a bit too much. That said, I really do understand people worrying when they are above. I have done this in the past, and probably would again.

David.