You are here

False Alarm

After being TFR for five years, although detectable at a very low level for almost all of that time, my PCR reading on 10/13 jumped up to 0.0356.  I was a little worried that I was on my way to possibly losing MMR (0.1).  I retested on 12/07 and my reading returned to a normal 0.0103 so I am surmising that the 10/13 reading was a lab error.

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

If I do relapse along the way (lose MMR, 0.1), I'll restart on Imatinib 100mg and reduce dosage from there.  When CML is at a low level after a TFR relapse, a minimal amount of TKI will suffice in suppressing it.  Most oncs/hemas still unnecessarily insist on restarting on full TKI dosage after a relapse.  That needs to change.

The less TKI we take over the longterm the better off we are likely to be.  Begin gradually reducing your dosage as early as possible to as low a level as possible.  .

Buzz

Buzz, glad you went back down and not up.  I know how even the tiniest increment causes alarm.  Your case is interesting because you've stayed TFR for so long without ever having been truly undetectable.  (I know, I know, not much of a difference. Still, I remember my onc, in answer to my questioning 'what really constitutes undetectable' answering, "Undetectable means "Undetectable"!)  Which, btw, at Hopkins means below 0.002%.  Anyway, the differences in all our treatments remain perplexing and troubling - my onc insists that I can't start my clock without a couple of years of true undetectable.  I have had a run of double zeros (not one, but two) to the right for about 4 years straight.  But nope, he won't do it.  In fairness, as you probably remember, each time I've stopped dasatinib for a pleural effusion to clear, my PCR has zoomed up within weeks to losing MMR.  Nine weeks was my best, but I wound up with a 2. something, which scared the bejeezus out of me - I hadn't seen that in 11 years!  I wish they'd hurry up and figure out WHY some of us can do TFR and some can't.

UPDATED: Kat, I don't want to mislead anyone, I neglected to post that I was "undetectable" for five years before I started TFR.  During that time I continually asked my onc to reduce my dosage with constant refusal until I said that I was going to reduce my dosage with, or without her help,  Still, after four years and ten months on Gleevec 400mg, the damage was already done; I should have begun reducing my dosage two years earlier; after one year of "undetected" status.  This is why I am a very strong advocate for gradually reducing dosage as early as possible.  It lessens the probability of suffering permanent damage from the side-effects of too much TKI.  Younger CML patients typically tolerate high dose TKIs better than older CML patients but that shouldn't be an argument to take the standard high dosage any longer than absolutely necessary.

see the following addition:

2012 U, U, U, U
2013 U, U, U, weakly positive
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 U, 04/18 TFR U, 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

I want everyone to know that losing "undetected" is not at all unusual during successful TFR attempts.

I often post the following STOP STUDY:
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.
Relapse After CML Treatment Discontinuation | Onclive https://shar.es/amW7LP

which is why, during TFR attempts, you don't restart until LOSS of MMR, 0.1 is verified and then you restart on the lowest dosage available.  The reason: when CML is at a very low level, common after legitimate TFR attempts, a minimal TKI dosage will suffice to quickly return you to your prior status.

Kat, how long have you been on Sprycel 20mg and what has your PCR reading been during that time?  You may very well be able to further lower your dosage without it having an adverse effect on your PCR reading.  It would be worth a try.  Six weeks before your next PCR reduce your dosage by skipping every fourth day, giving you an effective dosage of 15mg per day.  Typically there is very little change in the PCR reading; any minuscule increase usually resolves over subsequent tests.  The goal would be 20mg every other day for an effective rate of 10mg per day.

Buzz

I have same problem it's so hard to get medics to reduce. ..been on imatinib 400  for over 10 years now hit all the response milestones. I just see (well speak) to pharmacist for last few years But they swap. One who has since left asked me  a couple years ago if I wanted to go in STOP programme if course I said yes..Then nothing...Apparently there was discussion who would deal with monitoring if this eg Wirral where I am or Liverpool. Then all went quiet. I picked it up with my most recent pharmacist and  he said I had to be undetectable for min 2 years. Well that won't happen as I practically half the dose myself if not more as I don't like taking it all the time especially now it's the copies plus I agree it can't be good being full dose for so long  if there's no need for it. .  My most recent reading  is 0.001 and prior it's been around that or 0.003 for years and years . I've since taken advice here and asked pharmacist  if I can't stop I want to reduce. He seemed to think that was a reasonable request  but  to wait until new year now is my next review with pharmacist  to see What the consultant has decided. 

joflo, although not undetected, you can likely successfully reduce your dosage or even achieve TFR, and could have likely done so years ago.  During the Destiny Trial, 38% of CML patients who entered with stable levels between MR3, 0.1, and MR4, 0.01, were successful in their TFR attempt.  There isn't any reason you should remain on Imatinib 400mg.  I would suggest gradually reducing your dosage down to 100mg before deciding whether to attempt TFR.

Buzz, in answer to your question, I first reduced dasatinib to 25 mg in January 2018, then to 20 mg in June 2018.  All PCR's since April 2018 have ranged from 0.002 (Johns Hopkins' limit of detection) to 0.008, with 0.000 in March and November 2021.

Kat, you are in a good position to lower your dosage, with the possibility of a TFR attempt in the not too distant future.  It has been a long time coming.  

Wishing you the best,
Buzz

Thanks, Buzz, I think I'll stick at 20 mg for another year or two, then maybe try TFR.  I might do it by lowering the dose first for awhile.  Merry Christmas and Happy New Year to you, in TFR!

Hi Buzz,

Thanks for coming forward and showing your progress, and also for keeping track of other people's progress in the CML community. I've read your profile page in the LLS community website and find it very useful to see how many people have attempted dose reduction and TRF.

Best.

 

Thanks Israel.  The LLS discussion forum recently changed software again, unfortunately not for the better; in doing so internal bookmarks changed and many profiles were lost so my personal profile page is not quite what it used to be; sorry for that.

Most CML patients take far more TKI than needed raising the probability of permanent damage from side-effects .   I'm doing what I can to address that situation.  Not all CML patients will reach a TFR attempt, let alone be successful at it, but almost all CML patients can successfully gradually lower their dosage to very low levels, and do so, earlier in treatment.  I haven't yet seen a CML patient fail during a legitimate attempt to gradually lower their dosage. 

Neither have I seen a CML patient, who failed TFR, fail to quickly regain their prior status on the lowest prescribed dosage of their TKI.  After a failed TFR, CML is at a very low level; the lowest prescribed TKI dosage will suppress it.  Almost all oncs/hemas still insist on restarting on the full dosage of their TKI.   That needs to change.

The less TKI we take over the longterm the better off we are likely to be.

Buzz

Kat - When I decided to attempt TFR, I first decided to cut my 20 mg daily dose to every other day. And then every third day. Something to consider when you decide to try TFR. I did this as a way to wean myself off the drug and prevent withdrawal symptoms. It seems to have worked and I have been sprycel free for nine months so far. If I remain undetected at the one year off drug mark (March), that will be a major milestone - mostly because I will go to six month PCR testing instead of my current three.

I encourage you to try TFR when you are ready (at least 3 years undetected on your low dose). The sooner you know if TFR is going to work the better. There is no documented case of CML progression following a failed TFR attempt. All regained prior status upon TKI restart.

Thanks, Scuba, for the every other day method.  Glad to hear you're still TFR.  Are you actually getting back 0.000 undetectables?

My bcr-abl reports read  "undetectable".

For several years before I would receive PCR reports of bcr-abl < 0.01% and then it went to "undetectable". I remained at "undetectable" for 4 years while taking 20 mg, then 20 mg every other day (for about six months) before I stopped completely last March (2021). I can't tell a physical difference between being on drug or off although my joints are stiffer in the morning now than when I was taking dasatinib. Dasatinib may have been beneficial for arthritis due to aging!

Do I want to go back on drug for this benefit?

No.