I got my latest Jak2 update. The plot shows what is going on, a nice continuing reduction to 5%. My allele on IFN appears to be leveling off, suggesting a best value over time of maybe 6% if that had continued. The surprise is the steeper drop resumed on Rux. This continues to match my Dr's opinion that Rux is good stuff.
There are two members now reporting Rux VAF reductions consistent with the recent trial reports: Member Sewingtime has 60-25% over two years on a low dose.
I've held CHR on all three MPN meds; for VAF reductions on IFN having CHR is a correlation. I believe it's similar for Rux if I recall right.
Of course we can't know what my IFN would have led over more time. Same for future Rux readings. We have seen that IFN can reverse slightly to increase VAF at some point, usually on average after ~5 years, I'd guess Rux could do the same but it's not been studied this way yet.
As always, at what level if any does it matter? Could one go off Rux at very low VAF levels?
My test result has this note I've not seen before "The sensitivity of the assay has a lower limit of detection of 1% mutant alleles in a background of normal alleles, and it is not designed to distinguish heterozygous from homozygous mutations."
So if I have good fortune to approach 1% (unlikely) this test will start to lose accuracy. As in prior posts homozy associates with higher VAFs (50%+ for example) and responds better to IFN. This is probably why we see steep initial reductions here on IFN from the higher values. At 14% at Dx I more likely had heterozy.
Anyway I'd gladly trade some allele for Sjogren's relief any day.(not that there is any connection)
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EPguy, was the JAK2 allele level noted in a new bone marrow biopsy or through a blood work up of some sort? Glad these levels are sledding down the hill so fast!
All plotted ones are blood. I had a BMB at Dx that showed 19% vs 14% for blood. Dr said both are valid and as long as it's the same element it's comparable, makes sense. Anyway getting it each time by marrow would be a no fun.
Some reports found blood and marrow track closely, discussed in long ago posts, but otherwise is known as here.
Now if SS-a antibodies could do this I'd be back to life.
Nothing rational. Main reason is my bad luck of late. It's possible some of the herbals I'm using for Sjogren's are also helping VAF indirectly.
But this plot from an earlier post does support that Rux can get to near 0 for a signif portion of pts. It's the red bars showing 100% decrease at right. In this recent study BAT (blue) had ~40% pts including IFN, remainder as HU. Likely the blues on the right are mostly IFN.
I'm currently ~65% reduction all inclusive starting from 14%.
congrats on reduction in allele, I asked my expert at Mount Sinai recently if Rux patients can come off at some point like a minority of Peg patients, he said no, he said Peg and Rux do the same job but in different ways, hence he reckoned no point in combining Peg and Rux as they are doing the same thing. When they analysed my biopsy at Mount Sinai , they reckoned no MPN was detected, on closer questioning they reckoned the marrow result was one seen with Rux treatment, my allele was 20 and all markers and counts normal, and no other mutations present, I am hetero but unfortunately did not get NGS sequencing 6 years ago before starting Rux so no baseline allele.
Doing the same thing in different ways seems to me an excellent strategy, since "same thing" is never exactly that even using a same drug. IFN can be an exciting ride for some, count me in. One theory is Rux can take out some of that excitement, maybe I could have made it thru the vax incident on this combo. The combo studies used lower doses of IFN I recall, could be desirable. Drop in VAF was also steeper in one study I've posted.
Did they specify what marrow condition of yours associates with Rux? A recent thread included discussion of a study showing that IFN did not improve marrow for PV pts, while it did for MF. I've been curious whether Rux can have any effect.
Maybe you can get more VAF checks from now to compare the 20%.
Your note was "they reckoned the marrow result was one seen with Rux treatment, " This suggests there is a "Rux signature" that can be observed in a BMB. This would be neat info to know. My best guess from your info is VAF+ but histology normal (cellularity/fibrosis negative) and Rux was a reason for the negative. (this thought may be way wrong)
Agree on marrow with IFN; there was one report that found otherwise, with MF had greater effect. I'm trying to find it to recheck whether it was a high quality report.
What they meant was that my biopsy showed no evidence of MPN as a result of the Rux treatment, ie it’s not a cure but simply the condition being controlled by the Rux treatment, it took me a while to get my head round what they meant and I am still not 200% sure what it means. The analysis of the same biopsy by my local hospital in UK said similar , ie a marrow showing control by Rux. I will take that for now and see what next NGS and Jak 2 allele show this summer.
Hoping we can learn more from this info. It implies that among your Drs, Rux is known and expected to normalize marrow. Maybe this is their experience, and/or maybe there are studies. If so it would be a big deal. IFN can improve marrow also, but its effect seems unpredictable and not necessarily related to VAF response if I recall the various studies. HU has also been shown to do so ( posted years ago) but there are no follow up studies on that.
See here for a head scratcher: (VAF was discussed separately)
"Best bone marrow responses occurred in 17% of evaluable patients treated with pegylated interferon, compared with 33% of patients treated with hydroxyurea "
I wouldn’t say my docs expect Rux to normalise marrow, maybe more the exception as opposed to the rule. Mount Sinai did say they have a few Rux patients where the Jak 2 has gone completely, I know of one of these patients and she said she also lost other mutations allegedly
My take then is you got normalization, which is not common, but absent any therapy is not expected at all. So by default the Rux would be the reason.
Do you know whether these zero VAF pts could reduce or pause the Rux? My understanding is unlike IFN, that is not an option. Maybe with both normalized marrow and 0 VAF it is possible.
I think the experts have no idea how Rux cuts the mutation, but maybe there are reports on it. My guess is it's acting on elements other than the known mutations.
»If you think about reducing to a target of less than 10%, which has been shown by colleagues in France to be linked to your ability to stop drug, that was achieved by 21% almost of patients in the ruxolitinib arm, 9% of patients in the crossover group, and 3.7 [%] in the back group. »
Neat new info. She notes new a definition of PV disease can measured as allele burden.
Two items in that quote seem new: 10% being a cut off for discontinuation. Past reports seemed closer to 2% or less. "ability to stop drug"; the wording does point to Rux as being included. The report from "colleagues in France" would be good reading for more context.
I stopped IFN for three months at 8% VAF, PLT was trending up before I started Rux. So likely I could not have discontinued therapy; I'd guess Rux would not be better at 8%, if Rux has special advantage at <10% the "colleagues in France" would know.
I have posted on this part "...the best available therapy included some patients that were treated with interferon". If it's the same studies, the pts that had IFN in the mix (alone for with HU) was ~40%. The familiar red and blue bar plot above shows that study, the blue bars are one or both of HU, IFN.
But inclusion required non-response to HU so it seems biased to make HU, but not IFN, fail.
Great post, it’s a pity there wasn’t more data provided on how many patients were on which drug in BAT. I discussed Rux and Peg with my expert at Mount Sinai and he reckoned Rux should not be discontinued, he also was not in agreement with the French experts idea of coming off interferon due to low allele, he was more in favour with continuing Peg at lower dose or more spaced out.
Coming off interferon makes sense for patients who have some difficulties to deal with the side effects of this drug. Some are off IFN for over 10 years. It would be interesting to know the cost/benefit ratio of this approach on the health system, compared to phlebotomy alone or the BAT.
I think it's a report I've posted on. Of the HU/IFN mix there were ~40+% with at least some IFN. They broke it down better than that, it's in one of my old posts somewhere.
The Silver group has reported on the quit question (and countless other things) Their concern was persistent marrow pathologies that don't necessarily improve with VAF. Could be the 10+ year off IFN had marrow improvements too.
I agree with your expert. What’s the point to discontinue if the clone can potentially be eradicated…after 12 years of treatment :
« In the model, the number of malignant stem cell vanishes at year 12 for the patient shown in Figure 8. However, with a lower limit of detection of 0.01% the limit for detecting malignant cells is reached at year 7, while with a lower limit of detection of 0.1% the limit is reached around year 4.
Congratulations! I am very happy for your treatment progress. It is encouraging to see real data about what IFNs can do to make a difference. Thank you for sharing. Stay safe!
For completeness, this plot shows IFN and Rux, The later progress is on Rux. I think there is little data like this available. My IFN journey ended badly.
As I noted the IFN was on a flattening slope headed to maybe 6% while it steepened on Rux. (it may have steepened again on IFN, I can never try it again so can't know)
Isn't information just great! I'm so pleased for you, and a lot jealous! My wife had her Allele burden checked while in hospital in France, and that will be 6 years ago in May. It was over 70% never checked again since being in Wales. They just won't look at it here. The only numbers that interests the hospital is platelets and Hgb.
Seems worth a trip to London to find out if that's what it takes, but it's true knowing won't change any therapy. Is she on IFN or Rux? With IFN and possibly Rux, there's good odds it has gone down nicely. I seemed to be heading to a lowest possible on IFN (an assumption) while the Rux has taken it further.
She won't get a trip to London, as her hematologist has already said! She's actually on hydroxycarbamide and Anagrelide, but there's a chance she might start on pegasys in the next month or so. We are not too sure that a reduction in her Allele burden will make a big difference in symptoms unless it's an enormous drop, percentage wise. Thank you EPguy for all your input, it really does make a difference, as without your perspective and research, we'd all be pretty useless in finding much out.
On HU VAF reductions are seen only in the 1st 12-18 months after which it reverts to its likely prior path. This plot is in various posts including mine. So makes sense Dr isn't looking. But if she starts IFN not checking VAF at start and regular afterward is obsolete practice.
But there is some info, in old posts here, that HU can help marrow condition. This has not had follow up study I know of.
Hiya that's amazing that your alle has dropped! My partner has PV was only diagnosed in 2022 at the age of 32 but his alle frequency is 41% he's only on blood thinners and beta blockers at the moment, should he be on something to reduce his alle frequency? I don't really understand it that much but i believe the lower it is the better?
I am no expert, but consistently I see two things that are very helpful for most patients: having an MPN specialist and IFN. I am on Pegasys and believe it is helping me beyond the reduction in symptoms. I have no data to support that belief, just the experience of others on this forum. Best of luck to you and your partner.
Most Drs will select his treatments to keep blood counts in range. Implication is he doesn't need MPN type meds to get there. (HU,IFN,Rux...)
There are many posts here on whether also reducing allele (VAF) is useful. One message has been being under 50% relates to lower progression (old posts here). Some on IFN can quit therapy for extended periods but only at the lowest VAFs, less than 2% for example. So these could be examples of "lower is better". But some do well with very high VAFs.
But current thinking from some experts (the Silver Cornell group for example) is acting to lower VAF early in the disease is best practice. But marrow condition is also relevant and lower VAF may not correlate to improvements there (at least for PV on IFN, again discussed in old posts)
As usual no hard answers. But as patients, most like to have lower VAF if it's an option. My take is better to get it lower and find it didn't matter than not to try and find later it would have mattered.
Dear EPguy, I always look for your posts because you and Hunter delve into the science of MPNs and “cures”. You all make things clear to us. So very happy for your progress on Rux. It was new to me that it could do what IFN could do.
Now for a personal question. I need to take my COVID, FLU and RSV shots, but I’m hesitant because of your experience and others I’ve read about. Can one guess when to take them? Should they be together? I’m on every other week Pegasys. I can go three weeks between shots if I want to - my tests results hold their own. Your input would be very helpful. I really don’t want Sjogren's. My PV symptoms gang up on me, and I have days when I’m debilitated. Sjogren's sounds like it would be every day! Again, our congrats. You’ve had a tough road.
You're right this benefit for Rux is only recently shown. Partly because most early studies were for MF where reductions are more difficult. Luckily new Jak-i's are now avail for MF.
You're right that vax timing is newly relevant with much more than just one flu vax in the fall. I can offer a hard earned opinion of vax timing. At least two weeks apart, preferably more. I did one week and paid with my (good) life. At one week the preceding vax is near a highest level of immune activity, so the next one can overload.
Also among the mRNA Covid vaxes, Moderna has a higher dose than Pfizer (50 vs 30 mcg) Higher should be good for protection but implicitly is of higher risk. I got Moderna and a high powered flu vax a week later. An alternative is Novavax, is uses a different older tech; it's discussed on the Sjogren's forum as a possibly lower side effect option.
I'd also suggest vaxing farthest from IFN dosing, but with the long action of Peg IFNs this may have marginal risk benefit.
Agree you really don't want Sjo, except for thyroid, it seems to be the autoimmune that most associates with IFN (just my impression) For me it has been an emotional death sentence. I will post next week on more thoughts.
Thank you for your suggestions, and I know there are no guarantees, I’m trying to go 3 weeks and then have the Covid shot. We have a friend with Sjogren's, so I empathize. Emotional death sentence would be her description, also. I feel healthy in comparison. Congrats on your numbers. You certainly deserved some good news!
Agree on the healthy comparison. The MPN is just background noise in my case. The Sjo is esp aggravating because I actively did something to cause it, albeit FDA approved.
that is such wonderful news EP guy. It will probably make me be willing to consider rux if my platelet numbers don’t go down further on interferon. Be well,Deborah
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he's only on blood thinners and beta blockers at the moment, should he be on something to reduce his alle frequency? I don't really understand it that much but i believe the lower it is the better? 
