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Treatment Free Remission update

I have been off Sprycel since my pleural effusion at the end of November 2018. Last month my test was PCRU but this week it is 0.0099. 

I was hopeful to keep going without the TKI since I was MMR 3 months after diagnosis, June 2014, and stayed MMR and lower for the first year and then dropped significantly in the latter part of 2015 to numbers such as 0.0069 and eventually 0.0000 consistently since October 2017.

Obviously, if I stay off the drug, the numbers next month could be higher again. But, I have also read where low numbers are sometimes ok with TFR. 

It just seems that 0.0000 jumping to 0.0099 in such a short time is not a good sign.

Any thoughts appreciated. Thanks in advance.

Kali,

You are "o.k.". Nothing to be worried about at this point. ANY level below 0.01% is indistinguishable from PCRU. It simply is too low a value and in the noise of the test. In TFR trials, loss of TFR is not considered until PCR levels are greater than 0.1% (loss of MMR).

You would have to have a consistent trend upward in order to conclude that 'perhaps' you are losing remission.

There is a paper (which I am trying to find again) which reported that detection levels you show (i.e. 0.0099, etc.) occur in the general population. The PCR test at this level is full of false positives. The lab tech may have sneezed the wrong way and it skewed the results. In other words, you would have to have several repeated tests over many months of a rising PCR closer to 0.1% before "loss of PCRU" is concluded. Many of us will just bounce around with PCR numbers in the noise (not zero) and less than 0.1%.

However - in my case when I tested treatment free remission on my own, I went without sprycel for over nine months and my PCR did start to rise about 3 months later, but it never went over 0.1%. I was never PCRU in the first place, I was just curious if my immune system was able to keep CML in check. My trend was saw tooth - up one month back down again the next (0.01, 0.04, 0.02, 0.06, etc.). I could have continued this way  (and my doctor wanted me, he was curious too), but I decided to restart sprycel and see if it would have any effect. It did, my numbers fell right back over two months to < 0.01% and then to "undetected" where it has been. I will try TFR again soon (two year mark this year).

In your case, if your PCR levels rise another log or two, you might go back on low dose sprycel (20 mg) and test that your numbers reverse. It gives peace of mind. But at 0.0099 - 0.02 or so - just noise, or false positives.

Scuba,

Thank you for putting this in perspective for me. I feel better.

if you find that article you referenced, it would be good to read it.

Thanks!

Kali,

Here is one of the papers:

https://www.ncbi.nlm.nih.gov/pubmed/24535287

from the above cited paper, "While the bcr‑abl p190 transcript was not detected, the p210 transcript was detected in ~10% of samples. Notably, the incidence of p210 translocation was higher in males (12.2%) compared with females (7.7%) and males were 2.4 times more likely to have the translocation. A significant incidence was also observed in adults compared with children, where adults were 6 times more likely to have the translocation"

And with higher levels of precision, more non-disease people will show to have bcr-abl than the 10% cited above. I happen to believe that everyone has bcr-abl. Just in such low amounts that it is currently impossible to detect.

CML the disease is not dependent on having "one" magical cell mutating to produce bcr-abl and we get CML. I have mentioned many times that translocating genes produce aberrant proteins all of the time. Our immune system evolved to keep us alive long enough to reproduce and raise offspring to independence. Cancer (leukemia) is not a binary on/off condition. Bad cells are accidentally made all of the time. There is just some critical element (or cascading failures) in the case of cancer that sets an explosive population increase of those bad cells. Once established (like a flea infestation), normal methods (our immune system) no longer work.

I'm thankful for TKI's which put the genie back in the bottle for an overwhelming majority of us.

I have high confidence, Kali, that you will never deal with CML "the disease" again given your success to date. Hopefully you can remain in TFR, but if not, likely very low maintenance dose will be sufficient with side effects you can not feel to keep CML away for good. Someday there will be a true "cure" deriving from re-activating our immune system to keep CML below any measurable threshold without a need for TKI's. Within the next 10-20 years I expect to see that day come. Immune oncology is whose time has come.

Thank you Scuba! I appreciate the information and education you post on here so much. It is very helpful. Thank you also for the encouragement and your thoughts about all of this!

My onc sent message tonight and wants me to restart TKI, Bosutinib. Not sure what I think about that. 

Any thoughts will be appreciated. 

Kali, what has prompted the onc proposal to re-start TKI? As Scuba says BCR-ABL numbers well below 0.1% are noise, and unless there is a significant trend upwards these results can be ignored. The protocol from the Destiny trial in UK for TFR is to disregard individual results as long as they are below 0.1%. Hope this helps.

Alastair 

Hi Alistair,

Thank you for your response and question. His note said since it detected and I should go back on a TKI. 

When I talk with him today, I will ask him to read the protocol on the Destiny trial. I am glad you shared that with me. 

Did your PCR jump around too at the lower numbers?  I watched your talk when this forum shared the video and learned about your story and TFR.

Kali, yes my PCR jumped around a bit. The second last result during the year on half dose imatinib was about .02%, having been .0.000% for most of that period. Three months into attempting TFR my last two numbers were 0.000%. Prof Clarke's talk on Destiny at the patient day is well worth watching - much more important than mine!

Thanks Alastair! I will watch Professor Clarke’s talk. I appreciate the opportunity to learn.

Alastair,

I watched Professor Clarke’s talk about the Destiny Trial. It was excellent! Thanks for suggesting it.

Kali, glad it was useful. Best wishes Alastair