I just received back my allele burden and it has finally fallen from 14.5 in April 2024 to 8.45. It will be interesting to see what happens now since I've only been on the combination a short time. But I'm definitely happy with this. My HCT is still not under control, but things continue to trend in the right direction so hopefully some time in the next 6 months the phlebotomies will slow down a lot. Good stuff.
Updated allele burden on combination Jakafi & Be... - MPN Voice
Updated allele burden on combination Jakafi & Besremi
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Your mutation is following a path like mine (14 to 8% in 11 months) on Bes, although your HCT is still a work in progress. Mayne the combo is really hitting the spot. Good news overall.
What is you current dose of each?
Dose is 500 mcg of Besremi and 5 mg twice a day jakafi. So my dose is quite a bit higher than yours and it also took me since May 2023 to have an impact. Everybody is different though.
That seems quite a high dose of Bes but low dose of Rux, if you don’t get your Hct under control it is maybe worth discussing with your Haem about increasing the Rux , the typical start dose for Rux only for PV is 10mg BID, 60% need more and 10% need less. I am on 22.5+20.
Interesting and good to know.
I’m guessing most of my decline was from the Besremi simply because I was only on the Jakafi for only 3 weeks prior to the test.
I had been on 500 mcg for a while. Hopefully that comes down. Are you taking Besremi? You are taking jakafi 22.5 in the am and 20 pm? I wanted to make sure I understood.
Jakafi can take a while to kick in, not as long as Bes but usually more than 3 weeks, I am on Rux only , 22.5 in evening and 20 in morning, my AB is now allegedly 1.08%, all counts normal , no symptoms, so far so good
Wow 1%!!! Fabulous. When did you go on Rux? How high was your AB? If I remember right wasn’t it due to intolerance? More people should clearly be trying it much much earlier.
Unfortunately I dont have a base line for AB, they dont test it where I live, I started on Rux in 2017 at 2.5mg BID and built up slowly, most people dont need to start low and go slow as I did, I have a unusual intolerence to almost any drug but currently doing really well
Good thing on the 500 Bes, you are clearly well tolerant to it.
On VAF reductions, I posted recently the plot for my VAF thru Bes and Rux. Both have provided reductions so far. Maybe your plot would look similar in a year or so.
And after it, what happens?
Are you asking what is the effect of reducing the allele burden? Some studies suggest that lowering the allele burden reduces the chances of progression and/or complications.
In polycythemia vera (PV), allele burden refers to the proportion of blood or bone marrow cells that carry a specific genetic mutation, most commonly the JAK2 V617F mutation. This mutation drives the excessive production of red blood cells in PV.
A higher allele burden (i.e., a greater percentage of mutated cells) is often associated with:
• More severe disease symptoms
• Increased risk of blood clots (thrombosis)
• Higher likelihood of disease progression to myelofibrosis or acute leukemia
• Resistance to treatment
Monitoring JAK2 allele burden over time can help guide treatment decisions and assess disease progression in patients with PV.
Personally from the data I’ve seen, I think the impact is really critical. This is not entirely the opinion of my doctors, they would not fully commit to it. But after seeing the studies there is a pretty profound impact from keeping allele burden lower. Everyone is so cautious not to say anything as fact but it seems very clear to me lower allele burden is important, if achievable.
Can you tell us what method you have been using to discover your allele burden? I had a BMB way back at the beginning of my diagnosis but don't relish that pain again soon. I hear the blood tests are super expensive and hard to justify to insurers/Medicare, however, and that, as usual, comparing results of two different sorts of tests is tricky. Thanks!
This most recent time I had a blood test to determine allele burden. I have had 3 blood tests and one BMB. My physician team seems pretty capable in justifying the coverage by insurance, though it has been a bit of a battle each time. I'm in the US and the insurance varies obviously from carrier to carrier. I have to believe that the blood test is cheaper than BMB and you really do need to track allele burden since it's an indication of disease progression. Fight the fight if you can. For what it's worth my BMB and blood test allele burden results were extremely close to one another. I also saw a study that indicated they were also quite close to one another suggesting the blood test should be good enough here.
Chiming in to add that I recently had JAK2 and BMB allele tests done 1 week apart. Blood reported 8%, followed with 10% by BMB. Just notified yesterday that my medical insurance carrier (in US) declined payment for that blood test (a charge of $450). I've not seen my insurance refuse any payments in the past couple of decades. I switched hematologists, and unbeknownst to me when my blood drawn, new hematologist ordered another JAK2 test -- 4 or so weeks after the previous. Same result as first, 8%. I'm not sure how the repeat test will be justified to my insurance.
Yeah that makes sense based on the data I’ve seen. The blood test seems close. But now you have a fight with the insurance company over the $450.
I think you need to be careful with what you have written saying AB movement is a sign of progression, we don’t know that yet, there is no way a AB blood test is a comparable marker to a BMB
I found the first study- it appears to me that the blood test is comparable to BMB specifically for AB measurement.
pmc.ncbi.nlm.nih.gov/articl....
Specifically-
Furthermore, the JAK2 p.V617F allele burden measured in PB and BM were equivalent by linear regression analysis (R2 = 0.991; P < .0001). We therefore conclude that PB is a reliable source for testing for the JAK2 p.V617F mutation and quantifying its allele burden in patients with MPN.
There are a lot of very clever MPN experts , some of whom I have discussed the relevance of AB with and they say we don’t know yet how important it is,I know of a PV patient on venisection only for 30 years with very high AB but no symptoms and doing very well hence I would question some of what you have written
In your case I assume you still require the same dose of Rux to hold blood counts. Do you have any known other mutations? If yes to the first and no to the second, your results point to a lower relevance on blood counts for AB in your case.
I'm at 3% which is below some cut offs. I had no other known mutations at Dx. I assume I still need the same dose since my last counts were not esp low. If I get to 1% or less as we discussed before, my Dr is agreeable to try a reduced dose. The 30 year pt points to low AB relevance in the other direction. This great result could be an outlier.
Progression can be defined by change in blood counts, MPN related events or other things (marrow condition...) . My Dr said we would assume progression if my counts worsen while my Tx stayed the same.
Two recent Rux studies had AB vs events as a study endpoint and found it to be very relevant to event type progression as I recall and often posted lately. So median results point that way for Rux. IFN has no studies with this pre-assigned endpoint, so I think for IFN it remains more anecdotal if still suggestive.
My dose stays the same, I have currently no other mutations.
Changes in counts etc can have different causes and can go up and down for no obvious reason, my experience of discussing changes etc with docs is they will do a BMB to check if progression or change, my view from what I read and hear is BMB is the gold standard. Even in Oct at Mount Sinai my expert said we still don’t know what the importance AB really means. I think I wrote before he quoted fibrosis, he said for decades everyone thought the level of fibrosis was so important, he said now they have recently learned it’s not important at all.
I suspect having a lower AB is a good thing , however for example I read that if MF patients convert to AML (which is very rare) their AB can be very low, I havnt studied the science around that but it makes the point that AB is not as useful as a BMB and can’t be compared.
My Dr is the same, I'd get another BMB only if my counts showed a clear concerning trend change.
I have posted on that reduced importance of fibrosis. It's specific to reticulin, the less common collegen fibrosis is still a negative prognostic. Fibrosis is one of the key items checked in a BMB, so that would remove one aspect of the BMB from the prognostic. But cellularity and megakaryocytes are other basic items of interest, as well as a baseline marrow AB reading. Are there other findings you know of that are important in the BMB?
If you get the opportunity, it would be interesting to know your Mt Sinai expert's opinion on the fairly new Rux studies with the AB vs events endpoint that found signif relevance.
Hmmm, I'm curious of your opinion, even if AB is extremely low, and you are experiencing CH response are you of the opinion that it's worth getting a BMB every few years?
I agree with my Dr, another BMB only if there is a concerning trend or event in my blood counts or symptoms. VAF changes can be tracked easily via blood. He would order if I asked for one, but I don't feel a need for that experience without a clear reason. My Sjo overwhelms any MPN symptom signal I might get so I would likely not know progression from symptoms alone.
I've had CHR from all three of HU, IFN, and Rux so far. I actually had HCT and WBC normalize just after Dx on just aspirin if that was the reason. I've posted my plots that showed a rapid normalization just prior to HU. Except PLT, this requires meds for me.
This makes sense to me. If CHR, why go through it.
I know that is the opinion of a good number of people in the MPN community. However, life expectancy and quality of life data seems to be correlated to improvement in AB. Whether it is actual correlation or a by product of something else doesn’t concern me as much. In other words if AB reduction is the cause of the improved life expectancy, great. If it’s also not the cause but merely a byproduct of something else that is improving I’m not sure it matters. Something is happening that is slowly disease progression down where life expectancy is increasing fairly meaningfully. And AB reduction, even if it is not the cause of the improvement, seems indicative of things going in the right direction.
It doesn’t surprise me that there are exceptions to this- to your example of someone with a high AB but no symptoms. But those exceptions are not the masses.
AB alone isn’t a sufficient marker either. Ideally platelets, iron levels, HCT, and other measures all normalize.
I need to find the study which showed life expectancy against AB.
I just posted in another thread on the two Rux studies that made an explicit connection as a study endpoint.
I suspect having a lower AB is a good thing , however for example I read that if MF patients convert to AML (which is very rare) their AB can be very low, I havnt studied the science around that but it makes the point that AB is not as useful as a BMB and can’t be compared.
Perhaps there is another mutation contributing. I’ll look for that study next week. I may have saved it on my computer but I’m skiing for a few days. Very interesting conversation.
Interesting - What aspect of the BMB is better? I think of BMB as a way of getting information such as AB. AB is a piece of data while BMB is a way of getting data.
let me assure you there is a lot more to BMB than AB, just have a read of a typical BMB report, in addition there is a lot in how different experts will interpret reports and lastly most experts prefer to see the actual slides of the BMB and again different pathologists and docs will interpret what they see differently, ive been through that at Mount Sinai just last year
Here is a study presented at Ash in 2023 showing a big difference in prognosis from those with lower AB.
ashpublications.org/blood/a...
Also
pubmed.ncbi.nlm.nih.gov/336...
These demonstrate how remaining in the low risk classification has a profound impact on life expectancy- and disease progression.
Allele burden alone is not a perfect predictor of outcomes. However, it’s hard to ignore the strong case that lower allele burden, combined with the management of other correlated factors—such as hematocrit (HCT) control, spleen size, and platelet count—could play a crucial role in significantly extending life expectancy, slowing or even stopping disease progression, and improving quality of life.
In fact, a lower allele burden appears to be the strongest predictor of reduced complications and better overall outcomes in PV.
I think you're asking what my VAF did after the Bes period. I've posted this recently, it shows continued reduction to 3% on Rux.
vaf
Fingers crossed for you. I’m surprised your insurance carrier agreed to pay for both. I tried besremi for two years including the max dose for over a year and although it lowered my AB I never did get hct control and still had phlebotomy every two months. 8 mos ago I switched to jakifi only 10mg twice a day and have not needed a phlebotomy since and all numbers are good. My mpn doc, who is fantastic, said that for some reason the jakafi works for some when the interferon does not in terms of hct control. An added benefit of jakafi for me is that I no longer have the constant itching that I had with interferon. Best of luck.
This is what i'm hoping for! My Dr. just told me he is going to switch me from besremi to Jakofi.
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