I got a Jak2 VAF update Dec 3. It was 3%, down from 5% a year ago and 14% at start. The latest reading of 3% is a 79% reduction from baseline. See following post for my actual % data. I converted it to the units from Fig 1A of the Rux report here and made a plot, the red line.
My plot shows a faster reduction while on Bes and shallower on Rux. This is consistent with what we've discussed, IFN starts fast and levels out, Rux holds a more continuous slope. Interesting that the slope is quite similar to the blue trial results for the Rux period. Next year's result will be esp interesting, if it follows Fig. 1 my reductions will stop. Conversely if it continues down like this I'll be in the <2% zone that has been called "deep molecular response". I'm actually 3-4 weeks into the flat period of Fig. 1 blue, (~week 148) so maybe I'll get lucky and keep at it thru this period. But the Bes period may confound this timing.
HCT 43.8, Plt 400, Lymph 1.06(Low) Neut 6.62(High). This puts the N/L ratio at 6.24 which is prognostically undesirable for almost everything. I suspect it's from my ongoing Sjogrens deterioration and maybe leftovers of a cold I had.
I asked my Dr what if VAF goes to undetectable. He said we could try pausing the Rux. If I still have no non-driver mutations maybe that would work. We also had different recollections of why he ordered a higher dose of IFN than I wanted. He thought I was not getting blood counts on lower doses. But my plots show that 50mcg of Bes was enough. In fact he was pushing for max VAF reductions. Regulars know why I care a lot about this.
I asked Dr how his various other Rux pts are doing on VAF reductions, he said no one else asks for this test.
I may elect to switch to HU if it allows me to get into a Sjogren's trial or other access. We don't make choices or be too busy, we rather set priorities.
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EPguy
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Here is my absolute numbers VAF plot. Sorry I can't get it larger. It goes from 14%, 10, 8, 7, 5, 3%. I added a note "HU" at the left. From the recent thread with member SouthSideA a good reminder the early VAF effect of HU can be substantial. So that 14% might have been higher absent 15 months of pre treatment with HU. I actually don't have VAF for Feb 2022 as implied here, it was 15 months prior, at Dx.
It could be starting with HU is an effective head start for some, but I don't expect this has been or will be studied.
Thank you, EPguy, for what are always useful, data-driven posts and insight. For those of us just getting started on our MPN journey, I value your bottom-line advice to stick with IFN for as long as I can tolerate it and it manages my counts.
Can you please share what prompted you to switch from IFN to RUX? This switch seems to have worked well for you, and I wonder whether this is available to an early PV patient like me.
Do others have experience making the switch from IFN to Rux? And what has your experience been?
This is my post on my unhappy outcome that triggered the switch in meds. I've not read it in some time as it's too painful so I don't recall its written details. Bes otherwise was perfect, every blood count looked like I had no MPN at all and VAF was declining. But fatigue and esp malaise were bad.
It supports the low and slow approach. I've posted on data pointing to the median VAF on IFN starting to slightly rise after 5 years for other than the best responders. Both Bes and PEG have shown this. But the plot at top here also shows a leveling with Rux at ~3 years. But another study had 68-3.5% median VAF on Rux as in my other recent post. So to your question on including Rux, maybe a combo with Rux or a time sequence, as I have done, with each could overcome these trends if they apply. But I don't think any Dr would agree to creative options for an IFN pt with good counts and tolerance.
interesting info, re your doc saying you might pause Rux if AB is undetectable, I’ve never heard of pausing on Rux, I wonder if he has done that with other patients?
One patient on Rux who lost Jak2 asked her expert doc at Mount Sinai if she should stop Rux and he said no , allegedly simply because there is no data so far on anyone stopping Rux after losing Jak2. That is what she posted on MPN List forum , I didn’t discuss that with my expert at Mount Sinai so cant vouch for accuracy.
His idea was to watch counts, we'd know quickly whether I need to resume. Most likely he's not tried with others, I suspect it needs an inquisitive pt for such things.
My guess is maybe it's possible if there are no other mutations. At least a dose reduction should be possible. If no then we can say it's more evidence that known mutations are not the full story.
But I may need to go off Rux before we can find out.
On that Mt Sinai pt, was the NGS status known? Marrow fibrosity? (although I've read that reticulin fibrosity is not very predictive)
That other Mount Sinai patient did acquire some other mutations while on Rux but as usual correlation is not causation, I can don’t know re fibrosis but I don’t think she mentioned anything re that in her post, my expert at MS did say last year that they now realise fibrosis is not the big deal they previously thought it was.
Can the dose of Rux also be reduced further rather than taking you off entirely? My doc was concerned about long term exposure to Rux b/c of risks to skin cancers.
That is one of the options we'd consider if I get to very low VAF. For now my blood counts are not so low that reducing would be indicated. I agree less is better if it's possible.
In a separate current thread on Rux and Shingles, they found no correlation with shingles and dose which is strange.
Wow. What a great story to share through real data. Thank you for being open and honest with your journey. You are helping many of us to better understand living with MPN.
First off, this is great news. I'm absolutely thrilled for you.
No one else asks for the test because people don't know they should ask. It's disappointing that doctors don't want to track the data. Perhaps this is because by the time most patients are on Rux they are considered later stage in progression so it's not being used for disease mitigation at that stage. Thus the impact on allele burden is reduced.
I'd be curious to see the allele burden impact broken out by impact of the drug based on original allele burden to see if the impact is more pronounced if started earlier in the diagnosis.
I know that for myself, if my HCT doesn't stabilize I will absolutely be pushing to start Rux as well.
EPguy, your contributions to this group are invaluable. Thank you as always for sharing with us all.
Rux is only recently being considered for first line in PV, so you're right it would often come after other treatments have failed. This sets Rux up for a bigger challenge in some ways, most these pts are resistant/intol to HU or IFN for example. The IFN Rux combo is in my opinion what more PV pts should start with. It allows lower dosing/risk of each and the benefits of both. It could be good for your case to get the HCT.
In an older post I noted a report that Rux was less effective than IFN on VAF for baseline VAF's over ~50-60%. But as discussed elsewhere, most Rux studies have on hard to treat pts. I suspect as more results are avail for PV we'll know more on that.
Thanks for the encouragement. I often try to raise thoughts and questions for us to ponder and we all discover how rarely there are simple questions much less answers.
Is it now standard practice to run regular VAF assays? Do they have clear clinical significance? I've only had one genetic test, back in 2015 when I was first diagnosed with PV, when my VAF was 49%. Since then, neither my hematologist nor my MPN specialist has suggested doing another one. Furthermore, I don't believe that VAF assays (after the initial diagnostic one) are currently approved by my insurance company.
I think it's standard in only select practice groups. My Dr was all in on VAF reductions thru my Bes period, but since my crash and burn he's not interested. But I still am hence this latest result. In this post on Rux and others, it has been specifically demonstrated that VAF matters.
There is no equiv study for IFN with this pre set endpoint but the empirical evidence in many reports is compelling. Further various "less thans" are proposed, including 50, 10, 2% for potential benefits. The trial here had 2% being a magic number. "Undetectable" is a loose term depending on the test used. <1%, <0.1%. The Bes trial measured to 0.01%.
If you've been on Rux since 2022 a Jak2 test might show a nice reduction. I'm about to find out whether my Medicare Plan G covers the latest one I got.
Yes, I'm hopeful that an allele assay might show improvement. However, at my age (I'll turn 81 in April) the practical significance of this knowledge isn't so clear. In any case, as far as I know, my Medicare Advantage plan doesn't now cover it.
As a side issue, I'll be going for my monthly blood work in a couple of weeks, and I'm curious to see the effect of stress. My wife has been suffering from a metastatic liver tumor and is now in home hospice, in her final days.
Hi SBS_Patient - so sorry to hear about your MPN and your wife's difficult situation in hospice. I believe that stress is a factor in our symptom level and response to our medications, not based on any science, just my own feelings.
My MPN specialist did the original JAK2 VAF testing 3 years ago when I was diagnosed with PV but did not want to test again until after 2 years on Besremi. I think primarily due to insurance not reliably covering it. My second VAF labs were were just done in early December so the bill may still be coming, but I think they expected my insurance to cover it. We shall see.
You are in a very hard place and I wish for you the help that hospice can provide and the support of your friends and family. Take care!
Great news EPguy, down to 3% with lower VAF being the holy grail! Congratulations! I know you are dealing with other equally or even more tough auto-immune issues, but it's still good news that your AB continues to decline. Thank you as always for your detailed posts, they are always helpful and provide valuable inputs on our own journeys. I'm also happy to hear that Rux has continued the downward trend.
I was recently taken off of Besremi due to what seems to be an auto-immune response of hypothyroid and chronic hives, but equally disappointing, after a year on HU followed by 21 months on Besremi, my VAF went from original diagnosis 3 years ago of 22.0% to now 32.4% (no VAF results in between). I was shocked and didn't consider that it could go the other way. The research results always focus on the "success stories", not the other half. In any event I will meet with my MPN specialist January 6 and expect to start Rux, as well as discuss a half dozen lab tests to try to figure out the chronic hives. Fortunately mega anti-histamines and Singulair are keeping the hive breakouts and itching to a minimum (fingers crossed).
I'm taking your experience on RUX as encouraging, even though I'm not enthusiastic about going to my 3rd "miracle" drug. Hope you continue to get good news (and share it with us) on your MPN as well as your Sjogren's. Have a fun and restful holiday!
The "even more tough" is a good description, for me about 10x the misery of my MPN. As you say, something good is nice little lift.
Sorry to hear you could not keep up the IFN, a couple months ago you were still trying. Surprise that thyroid would force you off, but I'm sure you tried all the remedies. The hives were a trouble too it seems, which can connect to thyroid.
You're so right about the "success stories". We see numbers like "At six years, 20.7% of patients in the ropeginterferon alfa-2b group (n=19) achieved a JAK2V617F allele burden of less than 1%"
but that means that 80% didn't. And some went the other way as you unfortunately experienced. Note the 6 year report here also stopped displaying the VAF vs time plot that was in the prior Ropeg reports. They report a good but non-comparable result. The VAF starts to go up slightly after 5 years, wherein the better and lesser responders start to diverge. ( I've had hard time relocating this specific data, there is a report that had it buried but I goofed and didn't cite. There is also a similar one for PEG that is searchable and in posts)
In any case avoiding thrombosis etc is a top goal and our treatments do help with that. Many get good results with Rux on the PV itch, that may be different than what you have but hope is bright.
I'll also share any bad news too as I have done. My next VAF should be in a year and hoping I can defy that flat spot at 144 weeks (top image).
It's interesting that I've helped some here identify Sjo, and on the Sjo forum same for some with MPN.
Thank you for tour data summaries and the links you provide and also as important - your positive and proactive attitude. I read the articles more critically now and realistically with respect to myself. You’re right the PV/IFN itch is going away, maybe RUX will help with the hives too? And yes, we can’t ignore the importance of avoiding thrombosis, etc. That’s all good. Let’s keep up the good fight and try to have the best life we can as long as we can! Cheers!
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