I'm now 6 weeks on Besremi + Jakafi (5 mg 2x daily)
Today my WBC measured low for the first time at 2.83. Doc thinks these numbers have stabilized. Three weeks ago I was over 4.0
HCT was 41.1 up from 38.8. I will have to track WBC and NEUT # closely.
Have you done a phlb recently? If not those WBC and HCT give plenty of room to discuss a dose reduction.
Yeah, I had one 50 days ago and I have only been on Jakafi for 45 days. Given that the HCT increased from 38.9 to 41.1, I'm not sure that HCT is controlled. More to come in another month.
I was thinking of seeing what the data looked like in another month. The WBC is clearly low, though I'm unclear how low (how much at risk) it is.
Agree on that HCT status. Are your blood test including separate Lymphocytes and Neutrophils? In my last draw N is high and lymph trends low, this is a negative prognostic in PV and at least so far an outlier.
With separate N and L you can get better info on any dose reductions that could be required. With IFN, L more often goes low from experience here. My Dr used 1.0 as a min, I think Hunter's uses 0.5.
Yeah, my L has been hanging in the below range from 0.72 to 1.03 since mid 2024. However today it measured a new low of 0.66, which is obviously getting quite low. Doc's limit was also 0.5.
The N had been steadily in the normal range on just the Besremi ranging roughly from 2-4. However I was low for the first time today at 1.66.
Like WBCs I'm going to have to monitor these. I guess the question is whether it makes sense to reduce the Besremi or reduce the Rux.
I'm only on 5 mg twice a day for Rux, a low dose, vs. 500 mcg every 2 weeks for the Besremi, the max dose. However, Besremi is better at disease modification. What I am thinking is to wait 4 more weeks and get the follow up data to see if WBC/L/N move further. If they do, I probably need to make a change. If they don't I'm less sure.
At that time I will also be 78 days from my last phlebotomy. So if the HCT is around 45 (that's my average to the day for needing a phlebotomy), then that will also have an impact. But if the HCT is 43 or better that would suggest perhaps it is having some impact perhaps perhaps. I need more time/data to know. The other thing is my platelets dropped from consistently being 250, in the middle of normal to 180, at the low end of normal. Rux seems to take 12-24 weeks to have a more sustained HCT control.
It will be another 6-12 months before another AB is taken.
I suppose I probably lean towards reducing the Besremi to 400 to see what happens and then reduce it further ultimately to 250 or so to see if there's any impact, if needed. I want to see what the combination does. From what I've seen there may actually be a benefit from using both together. The Rux may allow the Besremi to be more effective.
Interesting that your N was high. I haven't heard that before, I don't think I've seen that yet on this board. Has that always been the case for you? Have you seen anybody else with that combination?
I also posted my RBC data. This data is quite noisy depending on time since phlebotomy obviously. But I am finally in the normal range. It seems plausible that the HCT would perhaps become more normal regardless of the Rux given the trend. This also may have accelerated from the Rux (black dot), it's still unclear with only 2 data points.
IFN is known on the forum for low L. You can see here over 4 years, my 11 month IFN period is the low yellows for L. Also note the high N at my Dx, In your case the IFN, given its known role, and the large dose you have, is a good place to look for the low L.
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High N is common in uncontrolled PV. But the reports on this alone trend to very old. More relevant and recent is the ratio:
"Neutrophil-to-Lymphocyte Ratio Is More Accurate Than Erythropoietin Level for the Polycythemia Vera Diagnosis "
ashpublications.org/blood/a...
where:
" NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR < 5"
nature.com/articles/s41408-...
So the low L becomes more worrisome if the N doesn't follow it down at some level.
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My last draw put me there, it's an outlier for now. I'd guess the Sjo has something to do with it. But I worry more about quality of life than some other outcomes.
Some of this may very well be noise. These numbers do bounce around a lot, which you've seen. Mine bounce as well. The higher N for you may very well just be noise since most past measures are right into the middle of normal.
Here's mine -
Pleased it working so well. What was your highest % JAK AB?
500 mg of Besremi is a very high dose, I was on 100 mg before autoimmune problems.
Will you now try to reduce Besremi whilst increasing Ruxo?
I was about to combine statins with Besremi and very disappointed I wasn’t able to try this out. According to Dr Hasselbach statins significantly enhance interferon effectiveness
My AB% was roughly 15% over a year and a half after 3 tests and then recently fell to 8.5%, measured 3 weeks after I started Jakafi, which would not likely have had an impact that quickly. So it was likely due to the Besremi. I'm hoping I can reduce the Besremi. Indeed I may need to given that my WBC is lower.
The statin comments from Dr Hasselbach seem to have a significant group of doubters. But I have it on my list to try if other things don't work given his clear interest. Why were you unable to try the combination? Have you been on just Ruxo?
Terrific! My combo of Rux and Besremi is working great for all my numbers except my Hct. It continues to be stubborn and usually by the time I get a CBC check( every 2 wks) it shows as being over 45%. Just happened a few days ago. I arranged for a phlebotomy and when they checked it before the procedure it was 43.3!I did take a dose of Besremi 2 days before. Even though my MPN specialist says that it takes longer to work, it did make it lower and I did not undergo the phlebotomy. This is the 2nd time this has happened. Glad, but frustrating. Thinking of changing labs. Anyone else have this happen?
For HCT, lab-to-lab variation are: ±2-3% due to different equipment/calibration. But there is also an altitude effect which can increase HCT by 4-10% in high-altitude residents. Dehydration also raises HCT, while overhydration lowers it.
I looked at some of your prior posts and your AB is high, as you know. It may be that because it was further along it is more stubborn to improve. What's your current dose of Besremi? I'm at the full dose of 500 mcg, but different people tolerate this drug very differently. How often do you need a phlebotomy?
Hi, My current dose of Besremi is 100mcg. My MPN specialist does want me to titrate up to 123mcg. I am a bit reluctant but will consider. Yes, my allele burden is very high and I am sure that plays into my struggle with Hct. I try to hydrate well before I go for check, yet that could be a factor too. I was doing g better with not needing a phlebotomy.y for 3-4 months but now it seems closer. Will be discussing all this in a few weeks. Thanks for your reply!
125 mcg
Wow, my dose is 4x your dose for Besremi. I'm 500 mcg. I'm surprised he doesn't want you at a higher dose. I didn't like going higher, but I didn't have any reaction to it specifically and my goal was to bring down the allele burden. Good luck!
Hello again,When I jumped from 50mcg to 100mcg I endured terrible headaches and then titrated down to 75mcg and gradually came back up to 100mcg. " low and slow". This approach has really helped me with this drug and will possible pursue going higher in dosage. Thanks for your input!
It’s not easy, good luck!
Greetings, and thanks for sharing your experience on Besremi with Jakafi together. Can you please share why you started both together? I ahve PV and am on Besremi alone and it seems to be working well. I'd appreciate knowing more about how you and your doctor arrived at this combination. Thanks for any reply.
Emerging evidence suggests that starting Jakafi earlier can help reduce allele burden (AB). Personally, I believe that AB reduction, along with complete hematologic response (CHR)—which includes controlling hematocrit (HCT), platelets, and other markers—is the best indicator of long-term disease control and prevention of progression.
It also seems clear that early intervention in PV leads to better outcomes. The sooner the disease is controlled, the easier it is to manage, and delaying treatment may result in cumulative damage.
Combining Jakafi with Besremi may provide additional benefits, potentially enhancing Besremi’s effectiveness. I’ve been on Besremi since May 2023, and my allele burden has finally started to decline (from 14.5 to 8.5). However, my HCT remains uncontrolled, and I still require phlebotomies every 78 days on average. On the plus side, my platelets have improved dramatically and are now within normal range.
That said, frequent phlebotomies are far from ideal. They intentionally induce anemia to slow red blood cell overproduction, which helps lower the risk of thrombosis in PV. However, chronic iron deficiency carries its own risks—fatigue, brain fog, hair loss, cardiovascular strain, impaired oxygen delivery, and other potential complications. Phlebotomies act as a temporary fix for the symptoms but do not address the root cause of PV.
My goal is to give myself the best chance at long-term, high-quality life by targeting the underlying disease process rather than just managing symptoms. Controlling HCT is the last missing piece for me to achieve CHR, and Jakafi is generally more effective at doing so. After nearly two years on Besremi, my need for phlebotomies hasn’t decreased or even slowed down—making me consider whether adding Jakafi could be the missing key to better disease management.
Jakafi does have its own long term risks. If I do get CHR, I will experiment reducing one or both of these drugs. But I would like to see if I can reduce AB to <1% and CHR.
Besremi Trial update 
besremi or jakafi
1 Year on Besremi results
