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Final results of DESTINY trial

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A couple of weeks ago, the final results from the DESTINY trial were presented at EHA (European Hematology Association).

You can find the abstract of the presentation here.

The key points were:

  • TKI treatment was de-escalated to 50% of the standard dose (imatinib 200mg daily, dasatinib 50mg daily or nilotinib 200mg twice daily) for 12 months, then stopped altogether for a further 24 months.
  • 72% of patients who were at MR4 at entry have been able to remain in treatment free remission
  • 39% of patients who were at MMR (MR3) at entry have been able to remain in treatment free remission
  • There was no difference in those at MR4 and those at MR4.5 at entry
  • It seems that initial de-escalation is not simply delaying recurrence, though the mechanism of its benefit is not yet clear. Possibilities include gradual mobilisation of leukaemic stem cells into cycle and/or gradual improvement in the anti-leukaemic immune response at a time when TKI is still present. These require further study.

For those who like a graph:

 

 

David

Thanks David for posting this. This is the best result so far for TFR!!! 

Another interesting bit where they cycled disatnib
@50mg every 48 hours and continued efficacy.

https://learningcenter.ehaweb.org/eha/2018/stockholm/215435/clemence.loi...

 

A world of wonder

Romo

Woo Hoo! Thanks so much for your summary David! 

The bit I love best is "There was no difference in those at MR4 and those at MR4.5 at entry". I've been trying to shift my MR4 for over a year and a half and it isn't budging. 

Makes a lot of sense that de-escalation is helpful prior to discontinuation. Just fabulous to have it published in peer-reviewed journals so that the medical profession will have confidence in supporting patients to de-escalate before stopping.

This is very good news, that 72% for MMR4 is a crazily high number, compared to the previous results.

The part about the utility of de-escalation is also very intriguing. Seems like bit by bit we are gaining a better undestanding of why and whem TFR works. If the idea is confirmed it might open the path for other approaches, aimed at mobilising LSC; I am thinking about Scuba's attempt at fasting, but I am sure there are other ways.

Thanks for sharing! 

 

Romo - Very interesting - thanks for posting this.  I'm only sorry that their cohorts did not include patients on 20 mg Sprycel, because now there will still be controversy over that low a dose (which is relevant to me.)  One of these days they will address 20 mg straight on and settle the question once and for all - I await this study, which I'm sure will come.  Also worrisome to me about this one is, I'd like to see how hard they looked for (or confirmed the absence of) pleural effusions.  With dasatinib, you really can't declare victory and go home on low dosing/maintenance dosing/intermittent dosing, etc until you can show a true benefit in not getting pleural effusions.  I mean, super hard clear data.  But, at least they're going down this road with research, so yay.

Very encouraging. Hard to believe that standard dose of nilotinib is still considered 400 MG 2X/day in this study.  I started nilotinib as my first line therapy 21 months ago at 300mg 2x/day and am now down to 150 mg 1x/day and have maintained >MR 4.5 for nearly a year.  So like Kat, I am also interested in studies like this at even lower doses before cessation.

The point about coaxing the LSC's out of hiding at lower dose is indeed very encouraging - hopefully this has happened for those of us fortunate enough to be able to reduce dose by at least 50%.

Kat,

My interest in this study coupled with the Destiny Trial
is in the Destiny Trial dose reduction possibly attributed
to LSC becoming  more active and therefore subject to TKI affect.
Or put another way,  'encouraged to come out of quiescent
start to divided and be killed by TKI.'

If that’s true then maybe drug intermitted therapy would do the same thing?
This all is part of Scuba’s theory about fasting.
Of course these ideas are for those of us in DMR.

For some folks the evil force of CML is more difficult.

We are all pioneers.

Romo