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Latest observations on TFR success with those who have kinase mutations

http://www.haematologica.org/content/early/2019/09/17/haematol.2019.2341...

This report is pre-publication and not widely released yet.

It summarizes observations in patients who have kinase mutations and were able to achieve treatment free remission (TFR) at the same rates as other CML patients without KD mutations. TFR in these KD cases were observed when patients were forced to stop therapy due to adverse events. 50% of them never lost remission. This is exciting news for those who may have failed a previous therapy and had to move to another TKI. The data listed is not statistical (not enough patients), but the observations are encouraging.

A key observation is that once a patient no matter the KD status achieves deep molecular remission ("undetected") for several years, the chance of TFR success is the same for them as for any other CML patient. I find this very interesting and good news.

Scuba what is your opinion about Tfr? The more you take tki the more chances you have to stay treat free reminsion? I mean is it better to take tki for 5 years than 3?or is it the same?

The DESTINY and EUROSKI studies both showed a positive correlation between TFR success and time on treatment as well as duration of DMR (deep molecular response).  In the EUROSKI trial, each additional year of DMR before TKI discontinuation led to an absolute increase of 2 - 3% in molecular relapse-free survival.  The data from the DESTINY trial (per Professor Clark who ran the study), showed a mean decrease in molecular relapse/recurrence of ~8% per additional treatment year over the 3-10 year range of treatment duration; however the recurrence rate for treatment duration of only 3 or 4 years is at least 50%, compared with under 30% thereafter.

Taken together, the results of these 2 trials strongly suggest that being on treatment for 5 years+ versus 3 years meaningfully increases the chances of TFR success.  Further, as shown by DESTINY, reducing dose to half of standard for 1 year prior to discontinuation also meaningfully increased the chance of TFR success versus discontinuation from full standard dose.

I ve read exactly the same! I am Mmr4.5 2.5 years. I reached mmr 4.5 after nine months of treatment with sprycel. I have decided to try tfr after five years+ of treatent

CMLJAX answered your question in terms of data. Dr. Cortes also mentioned to me personally that 5 years CMR is ideal for trying with two years being the minimal start point. The improvement over two years is incremental (see CMLJAX note).

So my opinion is - I am going to try NOW and not wait (now = in about two months or so). I will be at 2.5 years "undetected". If I lose remission, I will go back on low dose 20 mg dasatinib and start the clock over. I am not waiting an additional three years, because in my mind, if it is going to work, it is going to work. I have a 50 - 50 shot. The added few percent by waiting an additional 3 years is not worth it to me. I want to know that I can live free of this drug.

As it is, I am going to go through TKI withdrawal (joint aches - possible thyroid), I want to get through that sooner than later. In fact, I may just take sprycel once in a while when these symptoms show up in order to slowly wean off the drug. ... i.e. take it every other day, then every third day until none.

This is my opinion. The data cited by CMLJAX is the official line. You all know me by now - I follow my own line. Vitamin D!

I know how you feel. I feel exactly the same! I want to know if i can live without tki! But I will push my self and take them two more years and I will try tfr..!

Scuba:

I thought you have been on treatment a lot longer than 3 years, which should be in your favor. Good luck.  I know you will keep us informed.