My latest test results continue to show a reduction in JAK2 (56% to 24%) since I started Besremi in February 2022. The downward trend was slow at first, but I'm happy it continues to drop. I'm at 150 mg.
Jak2 and Besremi reduction : My latest test... - MPN Voice
Jak2 and Besremi reduction
Written by
Elizka
To view profiles and participate in discussions please or .
Read more about...
48 Replies
•
Good news! I am scheduled for my repat JAK2 Quantitative on December 15. Very interested to see what is shows.
Are there any paper which says to us that the VAF is important to test taking Besremi? Nothing found.
The papers do not necessarily address Besremi or Jakafi. They are focussed on the role of VAF in the presentation of MPNs. There is still debate about whether or how much VAF matters. I am of the belief that a reduction in VAF is a valid marker of sucessful treatment for MPNs. researchers like Moliterno support this. "The JAK2V617F variant allele frequency (VAF) is a key determinant of outcomes in PV, including thrombosis and myelofibrotic progression." ashpublications.org/blood/a...
My MPN Specialist is in agreement that VAF matters, Reducing it is a good thing; we just cannot prove "how good" yet. We are using VAF as a measure of successful treatment in my case. I expect that VAF will become a recognized endpoint measure for PV as more data becomes available.
Thank you Hunter! I also think of it this way: how can it not be a good thing to have a lower burden (perhaps less instability for transition?) JAK2 pulsing around in your blood?
I certainly look at it that way. So do many MPN experts, though not all are convinced.
I think Dr. Kiladjian summed it up nicely. "Please experts, help me... are there hematological malignancies where reducing the driver mutation is not clinically beneficial? I'm confused, this is disputed for PV and JAK2 mutation, so finding another example could be helpful... I can also take examples in solid tumors..."
Wow, GREAT quote. It is impossible to know the impact of all of us working together to help each other.
I'm about to start on my journey with Besremi; however, I'm not sure how they will measure my progress. My blood counts continue to be in the normal ranges..nothing high. Not sure what they will look for as in determining whether to stay steady with dosage or increase/decrease. Did you run into this during your Besremi treatment?
The primary goal is a complete hematologic response. That means that all three types of blood cells are within reference range. By definition, if we have PV we have erythrocytosis, which is the most important thing to control. The target is HCT < 45% or HGB < 15.0. Some differentiate the goal by gender HCT < 45% males, HCT < 42/43% females. Some with PV also experience thrombocytosis. The goal is PLT < 400. While PLT is a less important number than HCT, it is still used to determine what is considered hematologic response. It is also desirable for the leukocytes to be no elevated, if that was an issue. It is also essential to monitor to ensure that the blood cell numbers do not drop too far below reference range. This can be an issue with the leukocytes. Lymphopenia is fairly common on Besremi. You will also be following kidney, liver and thyroid function just to ensure there are no adverse effects.
The standard practice recommended by PharmaEssentia is to start at 50mcg and raise by 50mcg increments until a hematologic response is met or there are issues with tolerance. Not all follow this recommendation, preferring a low and slow approach, with a modicum of patience thrown in. That is the approach that I use.
Some MPN Specialists are tracking VAF as a valid measure of treatment success. I certainly agree with that approach. It will be up to you to decide if this is something worth monitoring.
Hope that answers the question.
Thanks, Hunter. There must be something they know to check when they treat patients with no 'out of range' numbers anywhere.
As I recall you have PV. I am thinking that you must be controlling the erythrocytosis with phlebotomies at this point. If no other numbers are elevated, the goal will likely be to keep your HCT/HGB at target without phlebotomies. They will tach to be sure nothin drops too low. Suggest you be very clear with your MPn care team about what your treatment goal9s) are and how you will monitor.
Yes, I agree. We have to have more conversations as to how they will monitor me. I am on no aspirin and never had a phlebotomy..my numbers were never high enough. If I had not had a BMT no one could tell I had PV. Maybe early stages of PV??
Did they give you your Jak2 allele% (VAF)?
With a normal biopsy the only reason for the IFN would be to reduce the VAF. But if it's already very low that reduces this idea, see quote below. Dose selection will be an interesting balance.
This discussion comes up in a quick search for Jak2+ normal bloods:
ashclinicalnews.org/mds-mpn...
The only quantified info is this quote " If the allelic load is >10 percent and the age >40 years, I would consider this patient at risk of thrombosis,"
The classic PV Dx calls or HCT over 49 male, 48 fem. "normal" for PV control is the lower numbers (45-42/43) Hunter notes. So you're under all of these and not increasing. It is interesting your Dr Rx Besremi. Did you have a BMB (marrow biopsy)?
You're likely one of very few or the only PV pt to be on Bes with normal counts absent treatments. Your journey should be smooth and will be great to hear how it's going. I have a one-of-a-kind status from Bes but not of the sort anyone wants to follow.
It seems your Dr is looking for prevention and VAF (mutation) reduction, a modern approach not common (or generally possible) in the past. Your dose likely will be set by keeping your blood counts from going too low.
I tended to feel better when HCT was not near the lowest of the range.
Thanks for your comments. I'm surprised also. I did have a BMB. If I didn't have a Jak2 mutation, not sure I would believe I had PV. Minor fluctuations on the blood counts over the past 1.5 years. No aspirin, no phlebotomies. Just hoping the Bes doesn't drop my #'s too low. Need to get clearer guidelines as to how they will monitor me and their goal for treatment before starting down this path.
This is a bit confusing. Your hematologist would not start you on Besremi in the absence of a PV diagnosis. If you are JAK2 positive but do not meet the diagnostic criteria for a MPN, then that is usually considered to be Clonal hematopoiesis of Indeterminate Potential (CHIP).
PV Diagnostic Criteria
Per 2016 revised WHO guidelines, diagnosis of PV requires requires the presence of either all three major criteria or the first two major criteria and the minor criterion.
Major WHO criteria are as follows:
1. Hemoglobin > 16.5 g/dL in men and > 16 g/dL in women, or hematocrit > 49% in men and > 48% in women, or red cell mass > 25% above mean normal predicted value
2. Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
3. Presence of JAK2V617F or JAK2 exon 12 mutation
The minor WHO criterion is as follows:
Serum erythropoietin level below the reference range for normal
I recall you had a surgery pending, I would want to be very clear about the diagnosis and purpose of putting you on Besremi at this point. Do you meet the above criteria or not? If not, then why would you take Besremi?
I have done quite well on Besremi and certainly support its use for treating MPNs. I would not suggest that it is without risks and side effects, however. Before taking Besremi, or any other medication, we have to be sure that the benefits outweigh the risks.
Hope you get all of your answers soon.
My BMB came back as: Roughly normocellular marrow with atypical megakaryocytic hyperplasia and mild reticulin fibrosis, consistent with JAK2 mutation-positive MPN. No increase in blasts, no diagnostic evidence of lymphoproliferative disorder. Presence of JAK2V617F .
I never saw my EPO measurement, so not sure what that was. At the time frame for the BMB, my Hemoglobin was 15.9..a week later 14.6; my Hematocrit was 48.. a week later 45.6. My numbers have been 99% great for 1.5 years.
Honestly, I have never been completely convinced I have PV, except for the BMB diagnosis. I do want to be clear how they will measure my progress if I decide to take this medicine. I very much realize there are side effects and want to be certain this is the right course for me.
I appreciate your taking the time to read this reply. I'm confused somewhat with these blood numbers and symptoms that could be caused by entirely something else.
Being confused by this is understandable. I would not be convinced about PV either. Suggest you get a second opinion from a MPN Specialist before you decide anything. I would ask very specifically about CHIP and maybe a very early stage of some kind of MF. Or maybe something else altogether.
Congrats on your results. I'm still taking HU but Besremi is the next step should things change. Appreciate the update.
Wow!!!
Neat progress. I recall your blood counts didn't drop right away on Bes, but have done so later. Does it seem that your VAF started to come down about when you got to CHR? This would match studies we've posted on before, getting to CHR makes reducing the mutation more likely. For example maybe you go to CHR around Jan 2023?
Anyway the path looks great.
You also posted before on dry mouth and eyes. Is that all ok now? or at least well explained?
Hi EPguy. I have been thinking about you. I do hope you are doing well. My WBC and PLT were impacted soon after starting Besremi, but HCT and Red blood cells started to get in line around April of this year which was 14 months after starting. I didn't know my VAF at that exact moment, but when it was tested again in June it had dropped from 51 to 33% which would correlate with my improved and "near normal" blood counts. Dry eyes don't really bother me, but I do add Refresh eye drops every night.
I'm doing ok, quite variable, thanks for the concern.
Having the HCT as the relevant marker in CHR for VAF reduction is familiar from what I recall in the various reports while PLT did not correlate so tightly. I'm not able to look deeper right now.
Good that your dryness isn't a big concern. It is a key part of my other condition.
EPGuy,
CHR, I am unfamiliar with term and the study you mentioned. If you have time, please share. Take care 😊
CHR is complete hematological response. Generally means red and white cells along with platelets are in normal range. The correlations of which of these to VAF (mutation) reductions are likely buried in supplements of various reports. I used to go deep into these and may have these noted in prior posts. Sorry that my health most times no longer enables me to do those things.
The broader idea of CHR relating to VAF reductions should be easy to find in my old posts.
I will dive in. Wishing you wellness my friend. Hugs Christy
That's wonderful news! Very happy for you. For info for anyone else here who maybe cannot get Besremi or interested in results on other medications, I have had v. similar experience on Jakafi/Ruxolitinib: reduction in less than two years from 60% to 25% mutant allele.
You have pleasant company in this success, just this year a report came out showing that Rux can provide this reduction for PV as does IFN. My Dr, who is pro Rux, was quite pleased to mention the new report. But it seems less effective than IFN for the highest starting VAF values with ~60% being a dividing line. (this detail should be somewhere in my prior posts) The post below discussed the new report.
Most prior Rux reports have been for MF where, possibly because of the higher starting alleles, the reductions were less dramatic.
I went from 14% to 7 or 8 on IFN, now on Rux for 7 months. My Dr may order a mutation test soon.
Really pleased for you!
Yeah!!!! Great news!!!!
Congratulations! This is great news. Thank you for sharing and offering encouragement to others. Stay safe!
Wonderful news Elizka,
I am so glad to hear of your trend. I too have Jak2, and take 150mcg since Jan 2023. My Specialist doesn’t want to test for a few years. But, at last visit said the plan would be to space doses from every two weeks to monthly. May I ask your frequency? Very pleased with Besremi, and grateful to those who share their Journey.
Christy
Hi there! Every two weeks. There is no discussion to move to monthly at this point in time. Thanks for the kind words.
Really great news! This truly seems to be the "game changer" for PV. Right now my MPN doc wants me to continue at only 50mcg because of recent side effects( headaches, rise in blood pressure). My allele burden has not been checked since my BMB earlier this year(94% ) I figure with being on such a lose dose and only on Besremi for 4 months, it probably has not moved much. I see my specialist beginning of Dec and hopefully the discussion will be that I can continue on this drug. Aside from that, has anyone seen a reduction is itching from using Besremi? Congratulations again!
Hi - My itching has subsided, nearly disappeared, on Besremi. I wasn’t expecting that, but I have to attribute it to the drug. Nothing else changed. I was on 500 McL for several months and am now reducing it gradually to get the platelets back into normal range. Good luck!
Hi,
You were on the highest dose and did not experience any profound side effects?? That's pretty remarkable ,if the case. My PLTs and Hct went up from trending down when I was on 100mcg, so hoping I can increase dosage with caution. Itching is my main complaint, it has definitely affected my quality of life, even though it mostly occurs after bathing. Hope you see a complete molecular remission going forward!
Good to take is slow and steady. Besremi takes time to work its magic so we have to be patient. I had itching prior to Besremi which I have solved with a nightly Clartin and lotion.
Hi,
Wish I could say that antihistamines and lotion would work for me. I tried Zrtec and just made me sleepy, but little relief. I use Sarna lotion after bathing and it relieves it a small bit. My MPN specialist suggested an antidepressent, Remeron, but I'm sure that comes with it's own side effects. I'll keep looking and hoping for more suggestions. Thanks!
Hi
That's a great result. Any side effects from the besremi?
Thanks
Hi! Only when I first started--increase in migraines. I somewhat resolved that issue with new CGRP drugs for migraines. I would have to say no beyond the first two weeks of starting Besremi.
That's great. Did you have any issue with elevated liver enzymes?
Maybe two times they were slightly elevated, but not consistently. I also didn't drink alcohol too often, but I completely stopped even having the occasional drink about a year ago and my liver enzymes have been normal ever since. I decided that my liver had to work a little harder since I'm taking Besremi therefore I'm not going to burden it with drinking.
This news is very good and exciting! Thanks for sharing that hopeful information. At the one year mark, my VAF had gone down but modestly. I’m hoping to see a trend like yours, and maybe that will coincide with getting the HCT in line. Like you, my platelets and WBCs responded quickly, and it took longer for the HCT to normalize. May the trends continue for you!
This community is amazing. It is so important to connect with others who are dealing with some of the same issues we are. So many times I have shared with my HEM insights from this powerful group of people sharing and taking charge of their health. Fingers crossed yours drops! HCT was the last to respond, but when it did it continued and I haven't had to have a phlebotomy for six months or more!
Wow!
same with me. I have ET CALR. It takes a bit longer to work with my mutation, but it kicked in during the summer 9 months after starting at. My doctor said it takes a while with some with others it is faster. Unfortunately, since it’s kicked in, I’ve been getting increased problems with pain in my body. Wherever I have had inflammation in the past, due to accidents or operations, basically with joints, I am really hurting it’s gotten so bad that I reduced last week from 200 µg down to 125. Lipina, still there, but much less. It is still not allowing me to exercise, and I wake up with pain and numbness in my shoulders, arms hands neck. Left foot.
a doctor diagnosed brain, inflammation in the brain stem and middle brain. I will gets given intracranial pulse to therapy for three weeks and I was feeling almost nothing. After I took off the electrodes in my ear and stopped that treatment. The pain came back, but only after I did my next injection. 😣
I am desperately trying to find a solution to this problem. I have read everywhere that interferon alpha causes brain inflammation. This makes sense by so many people are having depressions et cetera from taking. Besremi. Since it’s a new product, there isn’t as much information available regarding side effects as there is for the order products. My problem is that the hydroxyurea was causing massive neurological problems with me and the anagrelide has caused hard damage. I can’t go back to either of these. On Monday, I know how my bloods are, and then we can make a decision about further reducing Besremi. God please help.
HI,
Inflammation of the brain is something I was not aware of, but it all makes sense if this may have been why I experienced sudden development of excruciating headaches that lasted for 9 days. I had taken a 100mcg dose of Besremi 24 hrs before the onset. Maybe, maybe not. I will see my MPN specialist in 2 wks and this will be discussed. I did undergo a CT scan which did not show any abnormalities other than slight intracrainial arterosclerosis. The doctor did express an interest in doing a MRI and I may go ahead with it. Thanks for this insight. I hope for all your concerns to be resolved!
Good luck with it and Thank you.
Here is information regarding interferon, alpha to be and nutrient deficiencies. My MPN specialist is happy that I sent it to her. Once we get the deficiencies balanced out when taking any medication, side-effects are kept in check. 🙂
Not what you're looking for?
You may also like...
JAK2-Besremi big drop
With the slight increase in Besremi from 150 to 180-ish see previous post: https://healthunlocked
A Gene that affects allele reduction in Jak2 by IFN.
change or get rid of it before starting IFN. For sure it's not that simple since other risks are...
JAK2
Hi I've been tested for jak2 yesterday nothing was really said to me about it ive looked myself and...
Besremi and Hematocrit Control
months on Besremi and my WBC and PLT's are now in the \\"normal\\" range, but HCT control continues...
Besremi check with RN
down about taking Besremi, even having PV! Now, I'm one of two patients using Besremi in their...
Besremi being denied by Medicare
Besremi decision time
Besremi and Rux Combined
Switch from Besremi to Ruxolitinib
