Interesting Presentation by Dr Silver re long term survival on Interferons

[Paul123456]

vjhemonc.com/video/interfer...

He says he would take Colchicine as well as interferons! I’ll ask my Hems next appointment, I have JAK2 and TET2 (which reduces Pegasys efficacy) so always on the look out for something that might combat the ‘inflammatory blockage’ caused by TET2.

[EPguy]

Thanks for the discovery. It has some fresh looks at their long term IFN study we've posted about.

His comment on Colchicine I think is in context of CHIP (pre MPN state with mutations)

Notables:

-Plot here shows a lot more MF progression than we see in some other places. I believe this is without IFN, since he presented the familiar survival benefit that IFN provides. But this MF plot does match what we MPNs care a lot about.

-Marrow reversion needs at least 4 years

*This is the main actionable item: Low dose continuous "minimal effective dose". He's clearly advocating min effective dose and long term therapy. This low dose approach seems a recent emphasis and is quite different from many trials and some Dr practice.

-Non-drivers are a negative, he does not expand on what Jak2 only would mean.

-Inflammation needs fixing with IFN (See recent post on IFN-Beta re inflam. Not covered here)

Combos, he says this is likely future, I and others have posted often on this idea.

Marrow monitoring is rare in US, Canada. We should do it (note 4 year requirement above)

PV-MF

[GardNerd in reply to EPguy]

I’m interested in his comments about “low dose continuous.” In one comment, he seems to put that in the context of managing side effects by sticking with the minimum effective dose. Next time I see my MPN specialist, I’m going to ask him if there’s any evidence that going with the highest tolerable dose (even if it’s higher than the minimum effective for achieving CHR) could help speed up the time or increase the chances of marrow reversion. If that’s not a possibility, it’s hard to argue for sticking with a higher dose than needed.

[EPguy in reply to GardNerd]

I agree as noted, this is the big new info here. There is another report, I think by some of the same authors. I recall they said higher doses may benefit marrow reversion. But from this report it could be they have analyzed the data more and determined there is no benefit.

My Dr has been of the higher is better notion, but my dose is now capped at 140 by low WBC levels.

[Solyesh in reply to EPguy]

Interesting on the low dose over long periods. I just had this discussion with. my MPN specialist. He has been advocating something similar with his pateints. He has one patient who has been on IFN for 9 years now and is currently at a dose of 45 mcg every 3 weeks and will soon be going to 45 mcg/month. His opinion is that best to be at minimal levels always with the option to increase if need be.

[Paul123456 in reply to EPguy]

Dr Silver believes that we should always take interferons to maintain remission but this is the alternative view from Jean-Jacques Kiladjian

vjhemonc.com/video/h4t2le_z...

[EPguy in reply to Paul123456]

This must be where we've seen the <10% VAF reference.

He says two factors together: Min 24 months on IFN + less than 10% VAF holds 40% of pts in CHR (thus 60% do not hold CHR). 10% VAF is often achieved on IFN so this is good to know.

But this does not address marrow histology. The Silver Group is considering this additional factor which likely is more restrictive. By implication addressing marrow would require at least 4 years of therapy - while marrow reversion can happen on min required dose. This last item may be the big news.

[Paul123456 in reply to EPguy]

I asked about this during my last Guys Consult, from memory they said they are trialling/monitoring this but think they were advocating minimal dose as opposed to holiday. I will clarify next time

[FG251]

Dr Silver is nothing if not consistent! To have followed patients taking IFN for up to 45 years is an incredible contribution to the field. We hear, over and again, that PV is the ultimate phenotypic manifestation of JAK2, but I wish ET were thrown in as an aside as well. I can only assume that much of what he says (with regards to IFN treatment) applies to it, too - even if ET has traditionally been associated with a normal/near-normal lifespan, with a lower risk of disease progression than PV?

[EPguy in reply to FG251]

I agree. The deepest studies are for Jak2, at least bec it's the 1st MPN mutation and most common. My guess is most of the PV info should apply to Jak2 ET but the other ET mutation types may have unique attributes. I have PV Dx with ET features, so I am interested, and on Bes.

[FG251 in reply to EPguy]

Ah, yes - that probably explains why ET isn’t mentioned in some of these presentations, as he and others would have to issue caveats regarding CAL-R and MPL.

[Bluetop]

Thanks Paul -very interesting pieces