Had an interesting discussion with my MPN doc today. I have PV and have been on Besremi for 14 months and recently increased to the maximum dose of 500 mcg because we are not seeing the hct control we would like to see. All other labs have improved on Besremi but still requiring phlebotomy about every 10 weeks due to rises in hct. I asked what she is seeing from other patients on Besremi in terms of hct control. Interestingly she said that most women respond much better than men on interferons . She said most of her female patients respond better in terms of hct control both more rapidly and on a lower dose than men. She said it is not uncommon for her male patients, especially younger male patients to ultimately require higher doses and that she usually sees hct control in such patients but it takes a while and much longer than most of her female patents. I found this very interesting and wondering if anyone else on interferon has heard anything similar. I also found this reassuring since my goal is to eliminate the need for phlebotomies and am still waiting for that to happen after titrating up to 500 mcgs after a year on besremi. I’ve been at 500 mcgs since early February.
Variations in Patient Response to interferons - MPN Voice
Variations in Patient Response to interferons
How about your JAK2V617F allele burden ?
Had a bmb for use as a baseline prior to starting besremi a year ago and it was 40%. I asked my doc whether she thinks the percentage is relevant to how well we respond to besremi and she said that is unknown. I also asked when I could get a new test for the allele burden and she said insurance won’t cover it but that md Anderson would eventually test the allele to see if there was improvement from besremi. She was not clear on when or how that would happen. I do know that I got a bill for $3500 when I had the bmb so not looking to do that again soon on my dime even though I am curious.
This is the familiar allele result for Besremi. Your starting allele is right at where they measured. So when you do get a future result it will be easy to compare. Of course none of us match these "averages" but it's a fine reference point.
But you note your allele was measured via BMB. This is not necessarily comparable to the blood allele readings. Mine were 19 and 14% respectively at the start. So your best comparison may require another BMB although a blood result will compare fine for any large changes. This is worth discussing with Dr.
I've been ok on insurance, I have a good private policy. I got (blood) alleles at 6 month intervals while on Bes. But when I switch to Medicare things could change. Your BMB bill likely included all the pathology studies also so an allele-only via blood should be cheaper.
I have not heard of any gender-based response difference to Besremi. I am amle, age 67. I am maintaining a complete hematologic response at 150mcg. I have only had one phlebotomy in over 2.5 years. My allele burden has dropped from 38% to 9% in 18 months. I am responding quite well to a very low dose of Besremi, with only minimal side effects.
We really do respond to all of these medications differently. Perhaps at some point we will understand why. I suspect that the difference is genetically based. Hopefully we will learn over time.
Thanks for the response. I probably mistated what the doc said. I think her statement was more along the lines of when she sees a besremi patient with stubborn hct lack of response it is usually a younger male and by younger I think she meant young in the PV sense. I am 56.
my doc says that insurance won’t cover another allele burden test. Did you get a big bill when you had yours tested after being on interferon for a while?
It sounds like your doc has worked with enough patients on interferon to see a trend, at least in her own caseload. It will be interesting to see if her observations are supported in the follow up research on Besremi.
I have had no problems getting the JAK2 quantitative analysis covered. I did the last two 18 months apart. I have also done the more comprehensive Intelligen MPN Myeloid Panel that checks all three MPN driver mutations and a large number of non-driver mutations. I do not anticipate a problem getting it rechecked 12 months from the last time it was done.
I would not assume that just because your doc says that it won't covered that it won't be. With insurance companies, no does not always mean no. Sometimes it means you have to know how to ask and how to appeal. Bear in mind the researching how to file prior authorization requests for individual plans and filing appeals is time consuming. This is unpaid time for your doctor. Doctors can only afford to do so much unpaid work and still work enough billable hours to pay their staff and keep the lights on. This is where you can partner with your doctor as an effective collaborator. You can do research into the prior authorization requirements. You can also file your own appeals. If that fails, as the patient, you can take the appeal to a third party review.
I had to file my own appeal to get Besremi authorized. My doc tried and was unable to get it approved. After 14 hours of phone calls and filing the right kind of appeal, I did get it authorized. Getting labs approved can be handled the same way.
It is important to understand that many insurance companies have automated review systems that are set up to say "NO" automatically. Just because the rejection says that an insurance company doctor reviewed the request, it does not mean that a doctor actually looked at the request. There is an article that came out about this recently. Very interesting reading. propublica.org/article/cign...
We often have to be our own best advocates. It can be done when you are willing to learn how to do it. And have the time and energy to do so.
All the best.
I just recently stopped Besremi due to side effects (excruciating headaches). I started Besremi in Dec 2022 and had titrated up to 400mcg. The headaches started at 350mcg and got worse when I went to 400mcg. I had headaches everyday/all day and had to take Ibuprofen every 4-6 hours... It was impacting my life/work so I had to stop and I went back onto Jakafi. The headaches, thankfully have slowly been going away. My CBC counts weren't really responding quickly to Besremi but have immediately started coming down now that I am back on Jakafi. I was interested in the potential long term benefits of Besremi/Interferons however these headaches were too much. I wanted to share this info as there are so many potential side effects with Besremi and it seems like a total crapshoot as to if/which ones patients might get.
Sorry to hear that Besremi did not work for you. Thankfully jakafi seems to be the right choice. It is unfortunate that we are not able to predict how any of us will respond to the treatment choices. It is a matter of trial and error. Hopefully we will learn to predict how people will respond based on their unique profile. I suspect it is based in the genome. It is important that we share our experiences and that the data is gathered to help shape treatment in the future. Thanks for sharing your experience.
I also have had to quit Bes, you can see my post on it, a severe experience. But I had near perfect bloods on it and allele reductions so it's esp a shame. I'm also on Rux (Jakafi) now. As in other recent posts, Rux is better on allele reductions than known till recently, for PV. I hope to retry, but at lower dose and no more flu vaxes.
It seems you have a Bes dose that is tolerable, maybe more time at that could help. But your switch to Rux makes sense.
I believe part of my issue was that my blood counts weren’t under control when I started Besremi. If they where, I could have stayed at a lower dosage and not run into the side effects of the higher dosages.
Agree starting IFN while in range is good. I was there on HU and counts stayed about the same the whole time. I see your prior post that PLT was not in range on Rux. But now they are. Might open the option to retry as I will. But maybe being in range for a long period is best before trying again. I will stay on Rux for a while at least if all stays well.
Good to get some info from a real clinical use. Do yo know how many Bes pts your Dr's office is treating? As usual a high number would add significance to the observation. My Dr's office is now zero with me off the IFN.
I can't find any breakout by gender in the trials of IFN, although the Ropeg study did collect gender info. They probably could provide this from their large sample if they wanted to.
This male would probably be dead on a dose of 500. But the trials did use these high doses so it is well known. I was on 140 and it was too much, 75 would have been enough. More examples of the wide variations in response we see. It's great you are doing ok on the dose, and wishing smooth progress to the magic HCT numbers.
Thanks. Not sure how many patients and in fact she said something along the lines of “patients we are seeing”. Since she is at MD Anderson she could be referring to an ongoing study rather than just her patients. To me it was more of anecdotal comment but it took me be surprise. To Hunters point many males have a good response at lower doses so I think she was saying that when she does see a slow response to interferon it tends to be more prevalent in younger males than in women rather than an observation that women always have a better response. By young I assume she meant under 60 rather than the traditional “young” since I am 56. I think she was trying to reassure me that I will eventually get hct control and to stick with the besremi which I appreciated. I do worry about being on the max dose but am tolerating well so far and she says I can decrease the dose once we get hct control.
MDA is one of the best places to know these things so likely something to it. That is encouraging that you fit their pattern with a likely good Bes tolerance and outcome.
I'm like Hunter in the 60+ area, so we also fit their pattern.
Curious if your Dr has access to the Continuation PV study data to compare this detailed discovery.
Hi,
What is your age, were you recently diagnosed?
Thanks
Hi. I’m 56 so not young in the traditional sense but somewhat so compared to the average age of PV patients. I was diagnosed at age 50 via routine blood work. Treated with phlebotomy and aspirin for first five years and besremi for a little over the last year.
Hi again,
Have you experienced any side effects with the besremi?
being on the max dose since Feb isn’t that long and neither is 14 months from start . I know a patient on Peg for PV and it took him 2 years at 180mcg to stop venisecting, he maintains it now at 90mcg and is doing well. So even at a lower dose than 500 Bes you might get there with time.
I don’t know so much about Bes but certainly with Peg I have never heard or read the gender point.
Saw my hematologist Monday for a six month follow up. I’m a 74 year female in US/NC. She has over 50 patients on Bes and a range of other MPN patients. Started Besremi in December at 50 mcg then 100. Still also taking Hydroxy 3 days a week. Have had 1 phlebotomy since Oct, in March, HCT is now 41.5. Going up to Bes 150 next week. Minimal side effects, mostly annoying things. I asked about JAK2 blood testing and she said it may not be covered, and could cost $350. She doesn’t plan to test until after at least a year. I’m on Medicare with supplement that includes prescriptions. So that is one data point on cost, certainly better than $3500 for BMB. Wishing you good luck on this journey!
Thanks. All the best to you as well.
I’m curious as to whether besremi is covered by Medicare with supplement. I had to appeal to get Besremi covered on my insurance and was wondering what happens when Medicare kicks in some day.
I replied but don’t see it so hopefully this isn’t a repeat. I am in Medicare Parts A & B, but not Part D (pharmacy) … my supplement covers pharmacy. They agreed to cover Besremi - but the pharmacist at the hospital specialty pharmacy tracked down a subsidy by the manufacturer to cover my copay. Fingers crossed that continues. When you become Medicare eligible you can compare Part D plans and Medigap supplement policies to see which are the best for Besremi. It takes some time to research but would be worth it.
Great. Thanks
I am a 55 year old female. I started taking Besremi in December 2022. I have been advised by my doctor to continue to increase the dosage up to 500 as my HCT is not leveling off to anything below 46. The last dose I took was 300 and my HCT was 45.8 a week later. I am my first patient to use Besremi with my provider, although she is a MPN specialist. I hate the idea of continuing to increase the dosage, but that is what the prescribed method shows (and the doctor agrees). I have no major side effects that I know of. My goal is to stop phlebotomies ongoing. Since the HCT was under 48, we decided to opt out on the Phleb this month. My platelettes are lowest they have been (253), Iron could be a problem/low (79), RBCS are a bit on the high side.
We are on a similar timeline. I also started Besremi in December 2022, but I have also been on Hydroxyurea for over a year and started reducing that from everyday to now 3 times a week. Hoping to be able to continue less & less to get to zero and only Besremi. I am 20 years older so higher risk and have stayed at 100 Besremi but now going to 150 and likely higher over the next few months. I agree the thought of getting to 500 is a little scary and maybe that won’t be necessary for us (fingers crossed). Have only needed 1 phlebotomy in March since last October. Like others on this forum, my doc said that Besremi can take months to really start controlling HCT. I am also iron deficient right on the border with Ferritin at 7. Also she said the Proud study focused on HCT below 45 even for women, so while we are shooting for below 42 … we are being less willing to go for phlebotomy between 42 & 45. Interesting. There is so much to learn and so many variations. We’re all so different in our responses. I’m glad to hear that at 300 you don’t seem to be having bad side effects! Best of luck!
Sounds like your experience is similar to mine. Besremi did well to lower my platelets from 1500 to 500 hundred fairly rapidly but my hematocrit has been stubborn and I still have to get a phlebotomy approximately once every 10 weeks after a year of besremi starting at 100 mcgs and slowly moving up to my current dose of 500 mcgs. The PV playbook for docs is keep the hct below 42 for females and 45 for males due to risk of stroke from thick blood as I understand it. But the phlebotomies deplete iron which is why I started besremi to begin with after five years of phlebotomy only so I would like to delay if not eliminate the need for phlebotomy. Also my high platelet count supported interferon treatment even though I had not reached the traditional age of 60 which was thought to be the age to start meds for low risk PV pateients. My doc seems to think that now that I am on the max dose I will now eventually get hct control but in the meantime I continue to need the periodic phlebotomy to control hct. We are all different but I can’t help but wonder what causes the variation in patient response to besremi in terms of hct control. Hunter who is very knowledgeable on these issues thinks it is likely variations in our genome which makes sense. How our specific genome affects the aggressiveness of the over production of red cells by our bone marrow for different patients appears to be a key issue that still requires further investigation. I suspect that how early in the disease process one begins taking interferon may also ultimately be found to be relevant. However I am not a dr and these are just my personal theories . Best of luck to you !
According to chatgpt:
« How can we explain that the reduction of jak2 allele burden doesn’t always modify the hematocrit level ?
The reduction of Jak2 allele burden, which refers to the decrease in the number of mutated Jak2 gene copies in a person's cells, is often associated with a decrease in hematocrit levels in conditions such as polycythemia vera (PV), a type of blood cancer characterized by an overproduction of red blood cells. However, in some cases, reducing the Jak2 allele burden may not lead to significant changes in hematocrit levels. There could be several explanations for this phenomenon:
Heterozygosity:
In PV, the Jak2 mutation is usually acquired in a single copy of the Jak2 gene, making the person heterozygous for the mutation. Even if the Jak2 allele burden is reduced, the remaining mutated allele may still produce enough abnormal Jak2 protein to stimulate red blood cell production, leading to persistent high hematocrit levels.
Other contributing factors:
Hematocrit levels are influenced by various factors, including the production, lifespan, and destruction of red blood cells. Reducing the Jak2 allele burden may not be the only factor affecting hematocrit levels. Other genetic or environmental factors, such as mutations in other genes, bone marrow microenvironment, or hormonal regulation, may also contribute to the hematocrit levels and counteract the effects of Jak2 allele burden reduction.
Timing and duration of treatment:
The timing and duration of treatment to reduce Jak2 allele burden could play a role. If the reduction in Jak2 allele burden is achieved early in the disease course or if the treatment is not sustained over a long period of time, it may not be sufficient to fully normalize hematocrit levels.
Individual patient variability:
Every patient's response to treatment can vary. Some individuals may have a more robust response to reducing Jak2 allele burden, leading to a significant decrease in hematocrit levels, while others may not respond as effectively. Individual patient variability in the way the body compensates for the Jak2 mutation and the effects of treatment can influence hematocrit levels.
Compensatory mechanisms:
The body has compensatory mechanisms to maintain stable hematocrit levels. For example, even if the Jak2 allele burden is reduced, the body may respond by increasing production of other cytokines or growth factors that can stimulate red blood cell production, offsetting the reduction in Jak2 allele burden and maintaining hematocrit levels.In summary, the reduction of Jak2 allele burden may not always result in a significant modification of hematocrit levels due to various factors, including heterozygosity, other contributing factors, timing and duration of treatment, individual patient variability, and compensatory mechanisms »
Fascinating. My 1st time to see a GPT result on something I care and know a bit about. Matches what I've read on it. Satisfying content on 1st read, but not too specific.
I've not seen this data "even if the Jak2 allele burden is reduced, the body may respond by increasing production of other cytokines or growth factors that can stimulate red blood cell production" Any members familiar with this idea? If true it is interesting and worth more details and context.
But GPT is known for authoritative inaccuracies, might this be example of one?
I did hear that mentioned in one of the MPN Webinars but I do not remember which. I am inferring that the process is a form of homeostasis. The body is seeking to maintain the higher production of erythrocytes that is perceived by the body as "natural" for someone with PV. It seems that there is more to MPN molecular biology than the JAK-STAT pathway. That is inherent in the other kinds of medeications that may have efficacy for MPNs (e.g., LSD1 inhibitors, MDM2 inhibitors).
Interesting times to be in the MPN space. A lot is being learned. It was mentioned in today's PV webinar that the treatment options 10 years from now may be for more effective than what we have now. Good thing to hear.
Agree on the new stuff. Probably will accelerate. But to be available for our actual use then we would likely be aware of it now. Immunotherapy is known to us now and likely near a breakthrough for CALR trials soon, could be Jak2 is curable this way in 10 years.
There is some preliminary data to indicate it might be possible that was referenced in yesterday's PV Webinar hosted by MPN Advocacy & Education International. It will be interesting to learn more.
Wow. Interesting response via AI. Thanks for forwarding.
I’m up to 300mcg after 8 months. Very few side effects so far. Everything is coming down but hct is stubborn. I’ve had 2 phlebotomies in this time. Yesterday my hmt was 46, but I’ll get 300mcg Friday, so hopefully will come down in 2 weeks, otherwise another phlebotomy will be ordered. I’m a 82 year old female, & had previously only been on aspirin.
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