I was diagnosed at the end of 2020 with p-vera with the less common JAK 2 exon 12 mutation. I have been on pegasys for almost 4 years - now on maintenance dose. My doc told me I've been in hematological remission the last two years. I did the next generation sequencing genetics in November 2024 and my results showed my driving exon 12 mutation was now non detected in peripheral blood. This compares to 5% in blood and 35.3% in bone marrow aspirate that was found at diagnosis 4 years ago.
I am now considering a "pegasys vacation" for a few months (supervised by my doctor) as I have a rash which could be exacerbated due to the pegasys - not really sure if it will help but trying to eliminate possibilities. I know some of the European studies had people stop injections when they had reached a very low allele burden of the driving mutation. I was wondering if there is any experience of this and how it went and if anyone went back on pegasys/besremi and how that went. I don't want to take the drug vacation if it will compromise my treatment but the rash is troublesome.
thanks, Steve
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I discussed with Dr a hypothetical pause of Rux if my VAF continues down (last it was at 3%). There is no info on this for Rux, but IFN does have such claims from the Euro reports as you say.
NexGen is usually a broad look with sensitivity to ~1%,. In some labs and processes up to 1% VAF might rate "not detected". Do you have the precision of the test you got?
Your BMB allele was a lot higher, if you wanted to know with more confidence another BMB could be worth discussing, but that is a pain in both ways of the term. But as in a recent thread, BMB can hit or miss hot spots on mutation.
When I quit IFN my blood counts held for three months, yours might at least do that.
Do you have any more info on the rash? As usual any autoimmune reaction would be a worry.
Thanks for response. Oh yes, the rash is a separate rabbithole. It originated about a year + ago when my wife and myself contracted a mite from our elderly dog - then went through treatment over a year ago. Both are having some kind of "post mite treatment response" , mine seems to parallel hers but is much worse, kind of like eczema. Been through walk ins, primary care, dermatologist and now allergist - biopsies, predisone, clobestol, otc antihistimines, etc. Something triggered from the mite or treatment -could be autoimmune - I have bloodwork in the pipeline from allergist. Dermatologist seems to think its an environmental allergen but the story doesn't make sense. I did fine with pegasys for three years and only on low dose (45 mcg/every 2 weeks). Hence, with my wife and my reactions similar but mine more severe, at least considering it could be related to pegasys.
We used Quests Leuko Vantage MPN NGS test with 26 genes. AI says its high precision and papers seemed to indicate high accuracy. Other mutations found were reported to 0.1 % so I would think its precision is below 1%, but not specifically reported. One interesting result, it detected a new mutation that was not present 4 years ago (ASXL1 at 32.3%). Lab result reports it as driving mutation but I dont think thats right. some papers report a higher negative prognosis with ASXL1. Puzzling to me. It seems that if I was undergoing diagnosis right now, I wouldnt be classified as having PV (but maybe my blood levels would be fine so I wouldnt be tested).
You're right to consider autoimmune (A-I) as a possibility. A-I's can be triggered by many of the otherwise ordinary assaults on the body, virus/bacterial, Lyme, even shoulder surgery for one member of the Sjo forum. In my case a botched vaccine + IFN. Adverse reactions on IFN can occur at any point in the therapy and at any dose from what we see here. A pause could be worth discussing with your Dr to find whether something changes.
0.1% is a modern lower limit and not detected at that level suggests it's not there, at least in the blood test. Which brings up the ASXL. ASXL is known in MPNs and as BrightNorka notes it is generally a negative prognosic. This report discusses it in context of Rux.
"ASXL1 mutations (n = 14, of which eight had JAK2V617F molecular response data) were over-represented in JAK2V617F molecular nonresponders at 12 months (n = 8)."
meaning ASXL correlated to no Jak2 reductions in all ASXL pts who were measurable, and the ASXL pts had an inferior outcome. But you've had an excellent Jak2 response, so your case is an exception their Jak2 findings (in context of Rux) and if IFN is similar that could have a less unfavorable implication. As usual every case is unique.
I've posted a while ago on some research into AXSL treatments, none are in clinic yet, but there may be some trials.
Thanks for the info. I'll look at the AXSL treatments. It must be activating for something otherwise they wouldn't be studying treating it, correct?
It makes you think. So for the 4 years on pegasys my exon 12 mutation diminished significantly to ND in blood (not sure about bone marrow) while at the same time the ASXL1 mutation went from <1 to 32%. Are the two related? Is the interferon treatment somehow involved in creating the ASXL1 mutation- maybe the exon 12 mutation prevented it ? I'm sure I dont understand this....we have a lot to learn in the genetic realm.
I know from a report I posted long ago that DNMT3 can emerge during IFN therapy. This is another "non-driver" in MPNs and other diseases. That report was hard to quantify, you can find it in my old post. I don't recall a report on ASXL emergence, but your case is evidence it can happen. Our current mono therapies aren't known to reduce these other mutations, so as a minimum the IFN was likely not controlling it. Interesting theory on Exon 12 holding it down, but adding exon 12 back, if it were possible in would seem not useful of course. It also could be the natural course of the disease in your case.
I think most of the research is on combo therapies.
I can’t offer any real insight other than to comment on stopping and restarting Pegasys due to a rash / reaction that may or may not be helpful, but when I asked about this last year no one had any similar experiences. I have ET and been on hydroxy for 5 yrs, Pegasys was introduced and after day one ina rash started around the injection site that grew, was painful and itchy and then the bruising appeared (this lasted a month), two weeks after the first injection, I injected again on the other side of my stomach, the same thing happened, a week later I had a tonic clonic seizure after a week of having what I can only describe as spells where I thought my blood sugars were dropping and I was going to faint (I never did and I’ve never experienced this before). After a night in A&E and further discussions with Haemotology it was agreed that I had to stop the Pegasys and after a 2 month break we tried it again to see if it could have been the potential cause of the seizure which the prof felt was unlikely. The process was repeated with the same skin reactions and bruising, this time the rash started to blister, I just couldn’t tolerate it and we agreed that it wasn’t the drug for me, I’ve not had any real side effects with hydroxy and whilst it’s not dropping my platelets into the normal range it is maintaining them.
l’ve discussed a ‘drug break’ with my consultant and they’ve been reluctant for this to happen and I’ve taken on board there view point. open discussions with your team, lead by yourself should be encouraged and managed, could the dose be reduced and then stopped and then introduced again after a further period of monitoring. We’re only going to know the true effects of treament for us if this happens.
I hope you find some relief from your rash very soon (fexofenadine - an antihistamine is a great help if you don’t already have it in your (medicine cocktail)!
Thanks. Every story is challenging. Never had any injection problems. Tolerated pegasys well for 4 years. I take dose reduction very serious. LOL, fexofenadine is already in my cocktail....
Hoping to see more responses on this thread. It's thrilling to see that some have progressed positively where this is a discussion. The way I see it, the more on this particular thread the better.
Yes the science is going deeper into the disease. It seems that the proportion of mutated genes result in a proportional lack of control of the bone marrow blood cell making process. If you dont have any mutated cells left, what remains of the disease? I've seen mention of blood stickiness in MPN... Is that caused by something other than a mutation? I'm sure I dont understand this but will ask doc on my next visit..
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Guidance on % Allele Burden test
Anyone else experience worse side effects on Besremi as compared to Pegasys?
ET or MF?
