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TFR - You Can Do This At Home If You Read The Instructions

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I saw this on Facebook and thought the title was catchy.

Discontinuation Of Tyrosine Kinase Inhibitors In Patients With Chronic Myelogeneous Leukemia – You Can Do This At Home If You Read The Instructions

Charles A. Schiffer
Haematologica August 2019 104: 1508-1511; doi:10.3324/haematol.2019.222216

http://www.haematologica.org/content/104/8/1508?fbclid=IwAR1LHxS4W6C3QE8...

I don't think there's much new information, but here's their conclusion:

"To conclude, the report from the GIMEMA group confirms that TFR can be achieved in routine clinical practice and indicates that discontinuation be considered in appropriately selected patients outside the clinical trial setting. The relapse rate has been consistently in the 50% range in all trials, and future research should focus on the mechanisms by which recurrence is suppressed in the hope that new approaches, possibly immunomodulatory, can improve these results. In addition, patients should continue to be monitored to assess whether very late relapses develop."

Hi All,

I think that this article is worth a few comments on several bases.It is fairly well recognised by most clinicians that to be a candidate for TFR and discontinuation then one needs a fairly stable history of PCRs of less than 0.01% or MR4 and it is also recognised that the likelihood of not being able to hold the remission is about 50% of participants whether in a trial or otherwise on an individual basis. However it appears from other studies that  if one discontinues when at a level of MR3 then there will be lesser likelihood of maintaining the remission and would be likely to be down as low as 33% of participants.

If one looks on the home page of this site under Latest News Articles the recent study on"Descalation of TKI therapy before complete discontinuation" indicates that a de- escalation say down from 400mg to 200mg of imatinib for a period of time  before complete discontinuation  might lead to a higher level of remission-up to 67% of participants on trial over a 3 year period.

The title of the article cited here might be catchy but one presumes that no one would undertake to reduce or discontinue the dose at home with out clinical supervision and also without heightened monitoring and ideally monthly PCRs.

Another related issue is that of those that have to discontinue because of an intolerable side effect profile or need to do so because for instance they wish to commence a family and become pregnant or they need to undergo another course of treatment for another morbidity and the side effects are unknown or risky.In some instances patients may be in the early stages of their treatment and /or with an insufficient level of MR and of course this is a concerning situation

In a few weeks I will discontinue imatinib 400 mg for a period of 3 months after nearly 14 years on the drug  (and fortunately my PCRs have been nearly undetectable for a significant period of time) as I will undergo treatment for low grade prostate cancer in the form of implantation of iodine -125 seeds known as 4D Brachytherapy. My haema- oncologist has been in discussions with my medical oncologist and it is thought to be too risky to allow the combination of TKI therapy with highly targeted radiation therapy-the iodine isotope implants have a half life of sixty days so hence part of the concern.

We will have monthly PCRs and if there is a rapid loss of remission to worse than PCR 0.1% we plan to go on interferon alpha for a short period until it is deemed safe to resume imatinib either at 400mg or raise it to 600 mg in order to gain back a good response.Fortunately my prostate condition has been diagnosed to be in the early stages and the prognosis after brachytherapy is 95% survival for 5 years which is I believe is similar to that for imatinib and CML . In addition I will be treated at the Prostate Brachytherapy Centre at the Royal Surrey which number 4 in the world in terms of numbers of these procedures-they have not before treated a  CMLpatient with this technique so hence the unknown potential side effects.

Has anyone out there had to discontinue not by choice put because of  a specific condition or reason and did you regain your MR ? More specifically has anyone had any experience of having to consider radiation therapy at the same time as TKI therapy ? Has anyone had to go back on to interferon alpha for any reason and was it a success?

With best wishes

John

 

Thank you so much for this article. It is interesting to read about the suggestion for monitoring:

“monitoring of peripheral blood transcripts every 4-6 weeks for 6-8 months, then bimonthly for approximately one year followed by every three months thereafter for a minimal follow up of three years”.

I had to stop my Sprycel 50mg to let my lung recover from a pleural effusion. I have followed exactly this schedule. I am now at month 12 and will do a pcr test next week. So far, my numbers did not move, at less than 0.002 (detected but too low to quantify). 🤞🏻