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Dose Reduction- My Hematologists reaction

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So a funny thing happened this week....my hematologist wasnt that keen on messing with my dose of TKI as im stable and without huge impacts to my daily life. I started with a small dose reduction (400mg -> 300mg) while he was off on holiday and I told him this week.

His reaction was to give me the US guidelines /criteria for starting TFR and saying that he wasnt keen on dose reduction because its "indecisive" and i was left with the distinct impression that he thought dose reduction was a path lacking courage. He was pushing for stopping and doing monthly testing

I'm somewhat flabbergasted.

He noted that there are psychological factors with stopping (I'll say!) and I responded that i wasnt ready to go fully off yet for psychological and other reasons. But I really dont know what to make of his reaction...

There is apparently some evidence that if prior to dose cessation one reduces the dose say from 400 to 200 mg of imatinib for a period of time  then the chances of TFR increases-your hematologist is obviously not aware of this finding.

Most studies of successful TFR suggest that this happens in about 50% of cases-dose reduction on a prior basis pushes the success rate up it seems.I suggest that dose reduction all makes good sense because if you lose your MMR as a result of it, one is not going to then try to cease completely.

Regards

John

EvaH, by first reducing your dosage prior to any TFR attempt, should you fail TFR you can restart on a very low TKI dosage (Imatinib 100mg), rather than the full TKI dosage (Imatinib 400mg) that your hematologist would want to restart you on.   The odds are very high that you can successfully gradually reduce your dosage to Imatinib 100mg, or even less (i.e.,Imatinib 50mg by taking Imatinib 100mg every other day).  According to at least one Stop Study, age does play a part in TFR success; younger CML patients, those under 55, are less successful.  I've drawn the same conclusion from what I have seen.  

You are due to decrease your dosage to Imatinib 200mg shortly so you are well on your way to a much lower TKI dosage.

It's unfortunate that your hematologist is so closed-minded when it comes to dosage reduction as you could have likely began your dosage reduction years ago, after you had one full year of remission.

Buzz

Hi Eva
I think haematologists do fall into the 2 camps of either dose reduction or all or nothing. I asked my local haematologist about a possible dose reduction and his view was that i was close but not there yet but he thought it would be a total stop. I then had my 6 monthly appointment with my main haematologist and mentioned the same thing and again was told i was not quite there yet but the starting point would be to remove one of my tablets so going from 600 to 450 of Nilotinib. I wonder if it is an age thing as my local consultant is close to retirement and the other consultant was relatively young. Would that apply to yours?

I was very encouraged with the thought that after 18 years on TKIs i am finally close to DMR. PCR running at .01 with the odd one below that. Slow moving but it is still dropping even after this time.

Thanks for the comments, very helpful.

And yes my current hematologist is ancient. Past retirement in Europe most likely.

Hi Eva, not sure I agree with the age thing. Prof.Richard Clarke - the lead investigator of the DESTINY trial is now retired.

There is certainly a divide between those clinicians/researchers who advocated a Full Stop and those (in UK) who advocated trialing a lower (half) dose before any attempt at stopping.

As the original STIM studies showed, stopping in the first place requires stable deep molecular responses .... a sub-population.... successful long term TFR was achieved by another sub-population of that one.

The DESTINY study showed that people with less than MR3 or less than MR4 could maintain TFR, however what they were equally interested in showing (proving) was that a far greater number can achieve a significant dose reduction without the loss of molecular response. 

Whilst it is really great to aim for TFR, DESTINY showed a majority of those who have stable molecular responses can safely reduce their  side effects/AEs and costs etc with dose reduction/s, even if they fail to achieve TFR. In my opinion this approach is more likely to help the majority of CML patients.

Sandy