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TFR fail

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Hi Everyone,

I was wondering if any one of you have experience with failed TFR? How long it usually takes for dasatinib to start working again?

I was on 50mg of dasatinib and undetectable for almost 2 years, but i developed some rhabdomyolisys and my haematologist suggested it may be related to TKI so i ended up stopping all TKIs and got hospitalized. My rhabdo cleared up in about 2 weeks nicely, but it certainly was no joke. Both my arms swell up like a Michelin doll, and i put on about 8kg of water weight with the swelling and inflamation.  

After about a month without TKI my first pcr test came back with detectable brc-abl, around MR4 (0.0107). At this point we restarted 50mg dasatinib and tested again 2 weeks later, which showed a rather large growth of almost a full log to 0.085. I am a bit worried at this point… that is very close to losing MMR.

Do you think 2 weeks may not be long time enough for dasatinib to kick in? The growth rate is a bit alarming (logarithmically speaking). From ND to the edge of MMR in less than 2 month? I have heard some anecdotes claiming that younger people may get more aggressive response, and i’m 35. But still…

Is there anybody with TKI restart experience? I hope this episode didn’t completely wipe out that ~4 years of treatment progress that took me to get here.

Thanks in advance!

—Thomas

 

 

Thomas, I track TFR attempts on the U.S. LLS forum.  Since you became detectable in the first month of a forced TFR you certainly didn't have any depth to your remission.  I have only seen one similar case, a CML patient of your age who had been undetectable for almost eight years who tested at 2.0 after just three months of a TFR attempt.  She regained undetectable status five months after restarting her TKI.  

Is there any delay in between your testing and when you receive the results?

Hi Buzzm1,

Thanks for your reply. Yes there is a lot of delay between the test and getting the results. Before covid it took about 2 weeks, but for the past year it is more like 3-4 weeks. Here is a rough timeline:

Day 0: TKI stop

+4 weeks: PCR test #1

+3 weeks: #1 result 0.0108, TKI restart

+2 weeks, PCR test #2

+3 weeks -> #2 result 0.08

+1 day (today) -> PCR test #3 

Clearly the counts kept growing after i done the first test. Due to the quite significant lag between testing and getting the result i can imagine my counts may have even grew beyond MMR, and that 2 weeks of TKI before the 2nd test may have tempered that somewhat. I hope the next test will show a decrease.

Given your experience with TFR attempts what would be your suggestion? I imagine after this i should wait several years… is there anything that would worth doing?

Best regards,

—Thomas

 

Hi Thomas,

It seems that from the data and from previous studies that about 50 percent of us that attempt it will fail TFR; dose reduction prior to cessation seems to help a little though in terms of maintaining TFR remission though.

My experience is that in November 2019 I was advised to cease imatinib as I was scheduled to have brachytherapy for early stage prostate cancer (insertion of iodine 125 seeds into prostate ;80 in total).We were unsure of the interaction of the radiation therapy with the tki and little had been written on it.The story is that we rapidly lost our MRI about 2 months after cessation of the tki and by 14 weeks we were at 10 % on the PCR-we started again on the normal dose of 400mg but it took an awful long time to get back to below 0.1 which basically is safe territory. Essentially  we lost it in the space of 2 months from a previous undetectable and it took 14 months or so to get it back.My haematologist said that I was a bit slow in gaining remission and being highly experienced advised against upping the dose to 600 mg of imatinib -he said eventually it will come back.Apparently it is quite normal on cessation to lose an MMR fairly rapidly but to take a long time to get it back.

My situation is a little more complicated because we dont quite know what the impact of the radiation therapy would be on accelerating the loss of MMR and I guess that those CML patients say on radiation therapy for breast cancer might run a similar risk.The good news is we are fairly sure that because of early intervention that the prostate cancer has been zapped. However as for being a candidate for TFR in the future that seems to be a little unlikely at least not for some years hence I guess.

Regarding your rhabdomyolysis it is possible that the toxicity of the tki dasatinib cause your muscles to be inflamed and to disintegrate so hence the swelling;without treatment it would eventually be life threatening from kidney failure.Many tkis will lead to a condition called myositis or inflammation of the muscles (not as severe as rabdo). For both conditions the ck score (creatine kinase) will be raised so it might be useful to monitor this score on a regular basis in the future. I have to live with a raised ck and mild myositis plus non diabetic peripheral neuropathy basically because of the long term side effects of the tki. Mild exercise and lots of water to keep well hydrated seems to help.I no longer take a statin as that can lead to mucsle inflammation it seems .

So in conclusion for some of us cessation means that it is easy to lose MMR but quite difficult to get it back after restart.

Regards

John

Thanks, John for sharing your story. It must have been difficult to go through all the complications. I hope your condition have stabilized ever since.

Well, i guess there is nothing else to do but wait for the next PCR results and keep taking the dasatinib. A bit disappointing, but at least things can be managed. 

Thanks, John for sharing your story. It must have been difficult to go through all the complications. I hope your condition have stabilized ever since.

Well, i guess there is nothing else to do but wait for the next PCR results and keep taking the dasatinib. A bit disappointing, but at least things can be managed. 

Thomas, CML, untreated, can easily double week-to-week, so the three weeks in between the first test and receiving the result can easily account for the second test 0.08 result.  Not to panic, anything below 1.0 is considered to be a safe area.

It is unlikely that you will be able to maintain TFR but at some point in the future you may be able to further reduce your dosage.

Buzz