Prof Harrison discussing significance of reducing % JAK2 AB

[Paul123456]

Many of us believe that using interferons to reduce JAK2 AB can yield a significant prognostic benefit for some. However it appears that this may also apply to Ruxo although whether to the same extent?

youtu.be/WifYlSTmWn4(Not working as expected?)

[bruddery]

HAPPY NEW YEAR Paul. Thanks for this informative video clip. Janice

[hunter5582]

Was just discussing this issue with my care team. Different providers have different takes on the issue of allele burden. Good to see some more research on this issue. Thanks for posting this link.

[EPguy]

A top point is at the end, that "we're on the brink of molecular (VAF or allele burden) monitoring" at least for some pts. This is a big step to this new view from a top MPN expert, pointing to VAF being a goal that matters.

These studies are for Rux, not IFN. Studies for IFN would make even more sense since IFN tends to get a better VAF response. But there are plenty of indirect implications for VAF in IFN studies.

Here is one comparison of Rux/IFN

"Until now, complete molecular remission in PV pts has been described only in patients treated with interferon. Our data suggest that a subset of pts who present a rapid and sustained reduction of the JAK2V617F allele burden under ruxolitinib may eventually reach a condition of CMR with prolonged treatment"

sciencedirect.com/science/a...

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VAF vs Jak-i's will get more interesting with 2nd generation Type 2 Jak-i, discussed here:

healthunlocked.com/mpnvoice...

This one is supposed to get a better VAF than Rux.

[Bluetop]

Thanks Paul. Good to see research into the potential benefits of lowering allele burden. In the UK study, presumably 'best available therapy' was hydroxy. I believe you said in an earlier post that your allele burden reduced on interferon?

[violetta115]

I have been on Hydroxyurea 500 mg daily since 2020 and my Jak2 AB was 21%. One year later the AB is 12%. The 2020 result was from a bone marrow biopsy and the second result in 2021 was from a blood test. I was first diagnosed with ET, then PV and now MPN-U . I also have a TET2 allele burden of 42%. from 2020 BMB report . Can Hydroxyurea lower your AB? I haven't seen anything that suggests that.

[Paul123456 in reply to violetta115]

I’m the same, ET to PV to MPN-U. And TET2 plus JAK2.

Pegasys reduced my JAK2 from 80% to 12 % and TET2 from 50% to 40%.

And LDH from 230 to 100.

I think Pegasys works on a different level versus HU and is therefore potentially more disease modifying. At least that’s what those of us on Pegasys are hoping!

[EPguy in reply to violetta115]

It is likely you've have reduction. But some members have reported large differences between blood and BMB results. Mine was 14 blood vs 19% BMB. My Dr says we compare only the same method, BMB to BMB or blood to blood, and preferably the same lab.

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HU can reduce allele according to this report for Besremi's trial, but it is much less likely compared to the IFN. Control was on HU.

"After 6 years of treatment, JAK2V617F allele burden decreased to less than 1% in 20.7% of patients in the ropeginterferon alfa-2b arm compared with 1.4% in the control arm (P = .0001)."

onclive.com/view/ropeginter...

This plot shows the difference in median results. Most of us won't have this exact result but it shows the trend well. Since your allele was read after one year you would be in the area here that does get good allele reductions on HU. I was on HU for just over a year.

There are other agents that can reduce allele more than HU. These are Rux, and Bomedemstat that's in trials. But IFN still tends to have the best reductions long term.

Ropeg 5 year allele

[violetta115]

Hi Paul, thanks for your response. I've been doing well on the Hydroxy but my MPN specialist in New York has been encouraging me to switch to Pegasys or Besremi. He understands that it's hard to switch medications when you're feeling well with what you're taking . Its encouraging though to hear that Pegasys can also lower the TET2 AB as well as the Jak 2.

[EPguy in reply to violetta115]

If you're with Cornell in NY, they are the world's pioneer in IFN for MPNs. They saw the benefit before most others would even consider it.

[violetta115 in reply to EPguy]

Yes, I am with a wonderful doctor at Cornell in NY.