Tfr fail?

Eva, becoming.detectable during a TFR attempt doesn't always lead to relapse:

during the STIM2 Stop Study: http://bit.ly/1IbwZuh 2011
treated only with imatinib; MR4.5 DMR of at least 2 years duration;. median age 61, 62 men. 62 women
76 of 124 (61%) remained treatment free ... However 41, of the 76, lost PCRU without clear molecular relapse (loss of MMR). In this so-called-fluctuation group of patients, 7 were found positive once, 6 twice, 12 patients between 3 and 5 times, 10 patients between 6 and 10 times and 6 patients more than 10 times confirming that BCR-ABL reappearance does not automatically mean clinical relapse.

Personally, I have been TFR for over five years, and have been detectable for most of that time:
​2014 U, U, U, U (12/07 began dose reduction w/each continuing undetectable)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR
2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000
2018 01/16 TFR 0.0004, 04/16 TFR 0.0045, 07/17 TFR 0.0018, 10/15 TFR 0.0150
2019 01/15 TFR 0.0144, 04/15 TFR 0.0134, 07/15 TFR 0.0042, 10/15 TFR 0.0126
2020 10/13 TFR 0.0127
2021 04/15 TFR 0.0107. 10/13 TFR 0.0356, 12/07 TFR 0.0103

Clinical relapse is defined as exceeding MMR, 0.1.  

Wishing you the best,
Buzz

Any PCR value below 0.01% is indistinguishable from "undetected" in a pure statistical/mathematical sense. It is noise in the test. Many research facilities (e.g. M.D. Anderson) do not even report PCR values beyond two decimal points for that reason. Buzz is quite correct that loss of remission is not considered until PCR rises above MMR - >0.1%.

As Buzz's data shows, he is above 0.01 but below 0.1 and is 'positive' for CML, but his body is handling it without drugs. This is an ideal time for anyone in his situation to focus on immune system health (get those T-cells strong) so his body can take care of CML on its own. Presence of CML at these levels is not disease. Trend is important. Buzz is fluctuating within one log. Selenium, curcumin, magnesium, zero sugar, low carb (i.e. keto-like diet) all negatively affects CML stem cells which are needed to restart CML-disease. Proliferation requires weakened immune surveillance.

• https://www.researchgate.net/profile/Ujjawal-Gandhi/publication/26273482...

In your case, your PCR is less than 0.01%

However, 'detection' is always uncomfortable to see in a lab report when in TFR so I understand the concern. Stay vigilant and test again in 3 months. If there is a trend upward, you will likely catch the uptick and can act. CML is a slow disease in chronic phase. You will have plenty of time.

I would strongly encourage you to consider a new TKI and not go back to imatinib (e.g. dasatnib). The reasoning is that each TKI works a bit differently and attacks some clones of CML better than others. In this way, you attack what is likely emerging from TFR. And you won't need full dose to put you back in TFR. I went from full dose imatinib which barely worked in my case to low dose dasatinib which put me into "undetected" straight away.

Ok....well shoot if id known that in might have kept on low dose imatanib and not got for tfr :(

I had next to no issues with imatanib

Eva, if you do proceed to relapse, since you are dealing with a European onc, who wants you to change TKIs in that event, the odds are high that he/she will insist on restarting you on full dosage of that new TKI.  .When CML is at a very low level, such as after a failed TFR attempt, it typically only requires a minimal TKI dosage for the CML patient to regain his, or her, prior status.

Hoping you don't relapse, but if you do, be prepared to fight for what you want, which might include you restarting on a lower dosage of Imatinib.

Wishing you the best,
Buzz

Eva, the U.S. guidelines center around the requisites used in the Stop Studies, which, with the exception of the single 50% dosage reduction during the UK Destiny Trial, don't include anything about dosage reduction, especially the highly successful gradual dosage reduction.  During the Stop Studies, including the UK Destiny Trial, patients who failed their TFR attempt were restarted on the full dosage of their given TKI.

Although gradual dosage reduction has proven to be  highly successful and very beneficial to the CML community, not all oncs/hemas, especially European oncs/hemas have gotten on board with it.  The longer a CML patient is on the full dosage of any TKI, the higher the probability that they will suffer from the toxic side-effects.  Dosage reduction lessens the probability of side-effects.  After a CML patient has been either undetected, or plateaued, at a low CML level, for a prolonged period of time, generally, a year, or so, gradual dosage reduction can typically safely begin.  Not all CML patients will reach TFR, but almost all can safely reduce their TKI dosage to a very low level.

Restarting on a low TKI dosage, after a failed TFR attempt, is relatively new but I haven't, as yet, seen anyone fail to regain their prior status when doing so.  A few examples:

​tiredblood
prior to TFR attempt, on Sprycel 20mg

03/11/2021 0.164% :(
04/07/2021 Restarted on Bosulif 100mg/day
04/16/2021 0.128%
05/17/2021 0.025%
08/12/2021 0.000%

shweflen 
prior to TFR attempt, on Imatinib 300mg
11/17/2020 BCR-ABL:ABL = 0.026
11/24/2020 restarted on 100mg/day imatinib (onc recommended 300mg/day)
12/14/2020 BCR-ABL:ABL = 0.012
02/16/2021 BCR-ABL:ABL = 0.004
03/01/2021 started 100 mg imatinib every other day (record low 50mg/day dosage)
03/15/2021 BCR-ABL:ABL = Not Detected
05/19/2019 BCR-ABL:ABL = Not Detected

Debdoodah, on the U.S. LLS CML forum, will likely soon be restarting on Sprycel 20mg after a failed TFR attempt.  Note: she had been undetected on Sprycel 20mg for a period of years.

Lovely news Evah, I bet you are happy, Very happy! Reading what people here say about TFR, gives me some courage to start it myself.

I have been undetectable for 3 yrs, 20mg Dasatinib. Consultant suggested to start TFR in October, but I am not sure.

Do you Eva, Scuba, anyone, think I should rather reduced from taking 20mg daily, to taking 20mg every other day? I would prefer this, it is not as drastic as complete stoppage....

Thank you,

pigeon.

Eva, you are so right about the importance of being in a good place in our lives, before attempting TFR.

I reckon that our immune system is finely tuned to our emotions, and to our state of mind in general. It can be a friend or a foe. So, until I reach that happy place.....I shall just take baby steps and start with dose reducing, taking dasatinib on alternating days.

See what my consultant says, but I can tell you, I don't think I'm going to stop, not just yet.

My very best to you.

pigeon

Hi Denise, I was not aware that dasatinib comes in 10 mg doses. My consultant suggested  TFR, I am not too happy about stopping completely, and was thinking of taking dasatinib 20mg every other day.

I can see why you are  hesitant about TFR, it feels like our security rug is suddenly pulled from under us. As Eva said, she found TFR mentally quite tough; I concur, just the thought of it frightens me.

Could you please tell me a little bit more about 10mg dasatinib? I just checked and saw dasatinib 10mg comes as a powder for oral suspension, do you find it easy to take? I like the idea of taking such a tiny daily dose.

Thank you,

pigeon

Hi all

I cant say i noticed feeling better on half dose, i think my hair got a bit thicker at some point.

I started tfr in Nov 2021 and since March 2022 I've had a lot of muscle stiffness and low level joint pain. There are no inflammation markers in my blood so I'm assuming its related to the discontinuation of TKIs and I'm ignoring the discomfort mostly and trying to do stretching ever morning.

It might also be simply getting back to more physical activity after lockdown or maybe long covid - i never tested positive but i deffo had something viral and respiratory at the end of feb

Hi, I have been a bit of a rebel ,My Doc originally wanted me on 100 mg but I refused ,if a grown man of over 6 feet can be knocked off his feet with that dose ,then a little 5' 3 " woman like me would be floored for sure .I stood my ground with 50 mg for a short while and gradually reduced when I thought it was the right time for me .My Doctor always disagreed with me ,who is not a CML specialist .Fingers crossed it's working for me .