What is the percent of PV patients who progress to myelofibrosis and is interferon the only treatment available to lower the risks?

[Eferret]

I am taking hydroxyurea for my pv. From what I have read since I joined the group, there doesn't seem to be a way of confirming early the onset of myelofibrosis other than having regular bone marrow biopsies, which would be extremely expensive. For some people it seems the symptoms of myelofibrosis appear very suddenly. So theoretically, should everyone who can tolerate it be taking interferon?

[hunter5582]

Up to 20% of people with PV will progress to MF, usually after living with PV for quite some time. The estimates vary and individual risk cannot be predicted by general statistic. There are different variables that affect risk of progression, including non-driver mutations, length of time with PV, lifestyle, environmental exposures and more. It is possible that some would progress more rapidly than others. this could be for a number of different reasons.

Tracking PV status is an emerging area of the science of MPNs. It is worth noting that there is more to "progression" that transformation to MF. Increasing severity of symptoms is also a form of progression. Using a MPN symptom tracking system is one way to monitor your status. One symptom to be particularly aware of is splenomegaly. A steady increase in the size of the spleen would be something to pay attention to.

My MPN care team and I are tracking my PV status using JAK2 VAF as a biomarker. This is not standard practice but I expect over time it will become part of the tracking protocol. My JAK2 VAF has reduced from 38% to 10% and is holding steady there. I take that as a good sign. I am using Besremi for my treatment, which is effective for both maintaining hematologic targets and reducing allele burden. I have found Besremi to be easier to tolerate and more effective than HU, and my quality of life has improved.

The evidence is that Besremi can increase the odds of progression free survival. It seems likely that Jakafi (RUX) may have this same benefit. Both have shown the potential to reduce JAK2 VAF.

The idea that everyone who can tolerate an interferon should take it (or Jakafi) is a matter of opinion. It is an opinion that I share based on the data and my own experience with both hydroxyurea and the interferons. Not all agree nor have the same experiences. Note that there will be considerable resistance in healthcare systems due to the difference in cost between HU and the IFNs and Jakafi. Compare monthly costs, HU = $25.00/60caps. PEG = $4,200/4 doses, BES = $16,900/2 doses, RUX = $14,300/60caps.

HU and the IFNs are both recognized by the NCCN as preferred treatment options for PV. If Besremi is your preference, it is your prerogative to pursue that treatment option. You can expect resistance from your healthcare system/insurance company. They would prefer the cheaper option. It is up to you to decide whether to advocate for yourself.

Wishing you all the best.

[Innessant in reply to hunter5582]

excellent reply thanks hunter .

[EPguy]

From the current info both IFN and Jakafi (Rux) can reduce the risk of progression. Getting a molecular response (MR, reduced Jak2 mutation) is one predictor of better outcomes. And getting or holding proper blood counts relates to getting MR.

This was explicitly studied for Rux:

healthunlocked.com/mpnvoice...

The plot here is from that study. It shows a clear benefit for better molecular response and being MF free. DMR that had no progression was a mutation (VAF) of less than 2%. Another trial found similar results:

healthunlocked.com/mpnvoice...

The endpoint of being MF free vs molecular response was not explicitly set in the IFN studies but the evidence is at least as compelling.

So either drug has this ability. Certain other mutations make getting there less likely.

But your question "should everyone who can tolerate it be taking interferon". My opinion is yes. But many do not tolerate IFN long term, I'm one extreme example. Then Rux is an excellent option, although it has its own sides to watch for.

MF progression can show as a new change or trend in blood counts, rising WBC for example. My Dr has said we won't do another BMB unless we see such changes.

Rux

[ainslie]

the last time I paid attention to the stats conversion to MF was something like 10% at 10 years and 20% at 20 years, however I suspect these stats might be a bit out of date, clearly treatments are different now to 20 or even 10 years ago. Treatments such as Interferons or Rux may slow progression for a subset. May is the important word there. Generally very few of the experts will say that any of the drugs actually slow or stop progression. Hopefully they do and I suppose why not try them if no tolerance issues.

[EPguy in reply to ainslie]

I agree on the conversion rates. Until recently (last few years) most Drs considered it quite rare for the mutation to decrease, and we see this likely relates to conversion in the two studies above. My 1st hematologist considered a decrease near impossible late 2020. Now mutation declines are known to be not only possible but frequent among IFN and Rux pts. As more PV pts take up IFN and Rux the conversion rates should decline. We can hope for better answers for both ET and PV in the next five years or so as more pts are on these agents long term.

[ainslie in reply to EPguy]

Yes hopefully

[EPguy]

For your question specifically about IFN, this long running data collection from the Richard T. Silver Myeloproliferative Neoplasms Center is right on the point. This long running study has been reported in various forms and details and is a top source for the concept of long term MF free benefit with IFN.

ashpublications.org/blood/a...

You can see the large benefit for IFN out to 25 years. It is retrospective (looking after the fact vs a pre-set study endpoint), which is how they got such long term results. This makes the connection to better MF results directly, without specifying molecular response.

HU also shows some benefit over phlbs: "The PHL-O arm had a higher risk of post-PV MF compared to HU as well".

--

In the post below this easy to read summary comes from that report:

-Low Risk- (generally under 60)

--20 year MFS /OS--

INF: 84% / 100%

HU: 65% / 85%

PB: 55% / 80%

-Hi Risk- (Generally over 60)

--20 year MFS /OS--

INF: 89% / 66%

HU: 41% / 40%

PB: 36% / 14%

healthunlocked.com/mpnvoice...

IFN MFS