For those members currently on Besremi:
-What is the dose you are taking now?
-Are you in CHR (blood numbers in range) They used HCT<45, (w/o phleb male or female ) PLT <400, WBC< 10 to be in CHR.
-Is your dose still changing?
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This plot shows the doses used in the 3 year Proud-PV Ropeg trial. Most were well over 300mcg. (per 2 weeks) I think most of us are not at this level.
This figure is from the FDA's detailed analysis for approval of Bes which is (too) full of details.
Hi,I have been on Besremi for over a year and I am currently taking 500 every 3 weeks.
My most recent blood tests show that my HCT is now under control so I would consider my status to be CHR.
Assuming my HCT stays under control I expect to move to a regime of 500 every 4 weeks when I next see my consultant.
You are one of the few early Bes patients not from the studies. Quite the pioneer.
Your dose puts you equivalent to 333/2weeks, so that is in the lower area of the red boxes.
All this is just for background info, since I found this plot it seems interesting to see where we fit. Of course we all have very different responses.
I saw you were getting phlb, but seems the Bes has kicked in. If you can get to one month dosing you'll be near the time schedule they have at the 1 year point. At 500, that works out to 250 in this plot, which would be well under the red boxes.
Your dose is in the same range with ~65% of the trial participants from the supplemental data on the conti PV 5 year trial I've posted before
Have you had any issues?
Currently at 150mcg every other week. HCT and PLT at CHR. I only had mild basophilia prior to Besremi. Now experiencing mild leukocytosis (lymphopenia and mild neutropenia). It is questionable whether I could tolerate a higher dose due to immune compromise. If needed, I would try and look for ensure that NEUT > 1.0.
I recall you were potentially limited by the WBC. I may run into the same limit, but INF symptoms is my bigger worry.
In the terms of the trial, your WBC is in CHR since they define only as less than X, rather than WNL. "Leukocyte count <10 x 109/L" Doesn't mean it's good clinical practice.
They found WBC ranged from 2.5 - 9. Are you below that WBC total?
Are you and Dr considering any further increase in light of your response?
150 is in the lower tail of these plots. From the supplemental data on the conti PV 5 year trial, about 25% were in this 125-250 dose range. (65% dosed at over 250mcg and ~6% less than 125mcg)
WBC has not dropped below 2.63 at the lowest. The hemo-docs are actually most concerned about Neutrophils. DO not want those to drop below 1.00. The lowest they have dropped is 1.30. They cycle up to just about reference range and back down again.
HCT briefly popped up to 46.5 but upping the dose to 150mcg has the HCT back down to 44.5%. PLT are at 389. They have been consistently at target. So I am back to a CHR without phlebotomy. Hopefully it will stay there, but if my iron levels keep increasing I would expect the erythrocytosis to increase too.
I would rather bump my Besremi up a bit more, maybe 25mcg if I need to. See if I tolerate it without dropping the NEUT too low. We also discussed doing a mini-phlebotomy if needed. Hopefully that will not be needed since I feel so much better with my iron levels higher.
We discussed Lymph vs Neut before, my doc is consistent with yours. He said we have no back-up source for neut while there is plenty for Lymph outside the blood (Lymph nodes and spleen) The tension between HCT and WBC seems to be an issue for some of us.
I've got some room for more dose vs WBC, but being well within CHR at 120 :
- HCT 43.7, PLT 288, Lymph .093L, Neut 2.52 - (even the other counts no one cares about have normalized)
I still can't figure why Dr wants to keep going. I had at least short term CHR even at 75. All this seems broadly a good thing but it's causing me dissonance with Dr's plans. I'm currently holding at 120, he said it's ok if I still have INF symptoms to stay with that level but he wants to hit 200 minimum eventually. With my heavy symptom burden, I have been resisting.
Based on the plot here and our small sample, the trial was quite aggressive on dose. But both the trial and our small sample are dosing toward CHR, and no more than needed for that. I'm also surprised the trial didn't see more WBC trouble with the levels they used.
Besremi dose is 175 mcg every 2 weeks with CHR as you defined them.
The CHR definition was actually as used in the Besremi trial the plot here is part of. It does seem arbitrary in some ways and of course we and our Drs may use a different reference. My provider has a lower PLT limit.
One aspect missing in the trial is the "too much of a good thing" re WBC that some of us are seeing.
I’m not sure I’ve been on it long enough (just took 4th dose)
100mcg every 2 weeks.
Looks like great progress. Not quite to CHR but well on the way. In context of the trial plot here, you're on the uphill at 4th dose, so if you were in that trial it would still be increasing till CHR. Of course this may not be your Dr's plan or your best therapy, just something to compare with for how our med got approved.
Is your Dr planning to increase the dose, or let things keep moving down well as they are?
Do you have a Lymph result? This gets low for some of us.
I think she is planning on keeping it at 100mcg as long as there is progress. I see her next week. I’ll find out then. Absolute lymphocytes, is that it? 1.9. Normal range.
I have had a couple of phlebotomies I didn’t mention that. 2 in 8 weeks.
I like that plan, see my reply to Hunter. Have the phlb become less frequent?
It seems you have room with your WBCs (ANC and Lymph) to go higher if Dr decides to.
This was the beginning of ANY treatment for me. So Ive had Besremi , Phlebotomy, Besremi, Besremi, Phlebotomy, Besremi.
Only 2 phlebotomies ever so it will be interesting to see what my HCT will do.
On 50mcg every 2 weeks. All numbers under control.
Hi Orangeboykitty! 💖💖💖💖💖💖
That is below the lowest dose used in the trial, and quite a great response. I assume you and Dr do not plan to increase. You said you tried most the other treatments, did these not get you to CHR?
Yes, I tried most other things. I couldn't tolerate HU at all. With other meds, they usually controlled my numbers but side effects were pretty bad. The last thing I tried was Pegasys. If I could have tolerated a slightly higher dose, it also would've controlled my numbers, but when I tried the higher dose (going from 45mcg to 65 mcg) it gave me horrible diarrhea. Bottom line....the lowest dose of almost anything controls my numbers but if there's a side effect to be had, I'll have it!!
Currently on 400mcg but will be going to 450mcg this week. My numbers are still not stable and I’m still on hydrox pills until platelets are in normal range
I recall your PLT were not cooperating. Your Bes dose is right in the range used in the trial, but apparently higher than most of what we're seeing here. It seems to be working quite (too) well on the HCT.
Have you been able to ask your Dr about Anagrelide?
I asked doctor but he doesn’t feel like it’s a good time to switch because the goal is to get off everything and stay on Besremi only . Hopefully I’m almost there , I go for blood work tomorrow . My platelets were 565 two weeks ago, he wants them in the 400’s to start reducing the hydrox. Thank you EPguy , I can’t thank you enough for all you do here. God bless you.
I see my MPN specialist tomorrow and will report back then after the labs. I’ve had five doses, starting at 100 and the last one at about 225.
Current dose is 100mcg, CHR not yet within range but significantly improved!Before treatment my platelets were ~1300, currently sitting at 650. WBC was 9-12 and is now getting close to the lower end of acceptable. HCT has never quite been >45 so have thankfully avoided phlebotomy thus far.
I am 32, diagnosed with ET at 21 with platelets at ~600, and last year after further testing my doctors decided I am now more fitting with PV. Previous tried pegasys but side effects were intolerable even at low doses.
I have been on besremi for ~4months and am tolerating it okay at 100mcg with some side effects. We increased to 150mcg for two doses and had migraines and chest pain - both currently under investigation, but back on 100mcg in the meantime. Tried dropping dose to 75mcg on second-last dose but found platelets jumped back up, so holding on 100mcg for the foreseeable!
Increased side effects and low WBC are concerns with increasing dose any further - I have yet to see what impact it has had on allele burden but am interested to see if it has helped. My main interest in besremi was any potential slowing of disease progression, as at 32 I am not impacted by too many serious symptoms but I am concerned how much further things are likely to go if left untreated.
I do wonder after my previous experience with pegasys if perhaps I just can’t tolerate higher doses of interferon in any form&was wondering how the trial had everyone on such a high dose! But am somewhat reassured that it seems more of us on here are also on lower doses.
Good to have the right trend. You're running into a problem shared by some, getting to CHR brings WBC too low. You may have seen here that Lymph has good margin to go below range, but Dr needs to watch Neut carefully.
Some other members have had better tolerance on Bes over PEG as you do, but your history could be consistent with your Bes limit. At least you can get benefit from it while PEG didn't work at all.
I'm having similar issues as you with increasing dose. In my case I don't need more so I'm discussing with Dr. I think 100 is my max for no effects.
If there will be an allele burden benefit (AB) you could see it by the 1st year, and esp by 2nd year if it's following the possible path in this plot. The plot here is familiar to many members and shows Bes vs HU and its average effect in the study the top post image is from.
Is your Dr using 45 HCT as the max? In the US, standard practice in recent years for female is 42-43. Has Dr discussed this?
Yes, I can't imagine how I could have much more than 200 without obliterating at least the neuts! How long have you been on besremi now? Have you found the side effects decrease over time to any extent? I don't know that I've been on a stable dose long enough to really know if that will happen yet (besides the initial fatigue after a dose decreasing) but I am hopeful.
Dr is not using 45 HCT, was just reading off your base levels above quickly! I'm sitting at ~39, and wasn't much above that pre-treatment.
I will try to be patient for the allele response, but I do really want to see if all of this is actually having the desired effect. That said, I'm very glad there's a long game to play versus hydroxy!
HCT 39 is nice and low. Has your Dr explained what is pointing to PV? Usually PV includes raised HCT, that is in fact one of the WHO criteria.
It seems your dose is driven by PLT, while many have HCT driving it. The good thing there is by most references PLT up to a point is less often a risk factor than HCT, so that might give more room for adjustments.
I had the early flu like effect with Bes, but it was no big deal and have no longer. But the bigger trouble, malaise, continues at 6 months and seems Bes dose dependent. I also have a weaker body, and this corresponds closely to the start of INF. In general more very bad days on Bes than I had on HU, but I'm still game for the long term benefits.
Hi Clara! Your the first person that has responded regarding Pegasys side effects being intolerable on the lowest dose but you appear to be handling the Besremi okay. I was on Pegasy as well at 22.5 which is so low that it wasn't very beneficial ( Had ALT-liver problems on 45 dosage) and was still experiencing horrible brain fog with some depression thrown in there. I am considering going on Besremi after I get my recent BMB results back. Could you please tell me what your side effects were on Pegasys and how you feel on Besremi? How different are the 2 drugs for you symptom wise and did you have rising ALT/AST levels on either drug? I'm PV diagnosed 18 yrs ago at age 43. Currently am taking 2 aspirin a day....with Phlebotomies every 3-4 months. Feel I need to be on something to address severe anemia but I'm a huge lightweight on ANY drug! Thanks for your comment. Kerry
Yes! I was quite nervous about besremi because I had such a bad experience on peg, but it has been working out better for me.
I can't actually remember my Peg dose now because it was around 5 years ago and I wasn't planning to revisit it! I had bad flu-like symptoms and fatigue for two days after each dose, which eventually was reduced to just one day but made it impossible for me to go to work that day. I had a lot of dehydration side effects (constantly thirsty, such dry eyes I had to stop wearing contacts and get eye drops, perpetual sore throat), constipation&stomach aches, as well as general fatigue and brain fog, and I also suffered depression within a couple of months ended up on antidepressants for around a year afterwards.
Besremi has been significantly better at the lower dose - the day after each dose I have some fatigue and symptoms as though I have minor allergies, but this reduced after the first two doses and is nothing compared to the peg. Initially had stomach cramps, constipation and dehydration for the first several days after a dose but this has also improved and I now just have a couple days of minor stomach upset. Thankfully my mental health seems so far to be intact!
At a higher dose I had more problems - I suffer from migraines on average once a month, but with an increased dose I had 1-2 per week, which was pretty miserable as they last 2-3 days each.
I also found that around the start of treatment I began to have chest pain with intense exercise, and once while on the higher dose I ended up in the ER out of concern of a heart attack. Fortunately they found nothing, and I am currently under further investigation to discover whether the pain is medication-related, disease-related, or entirely different. The timing of onset is certainly suspicious, but I did briefly experience something similar many years ago so it may be merely exacerbating an existing issue.
As for ALT/AST - currently doing absolutely fine on besremi, and to the best of my recollection with peg there was some change but not to a concerning level. I'm not able to check my exact results for it as this was in the UK and I have since moved to the US.
I hope some of that is helpful!
Thank you Clara for the detailed account of your reaction and symptoms on both INF's. Your reactions to PEG are very similar to mine. On a PEG dose of 22.5mcg, I was still experiencing very unpleasant symptoms. Lack of quality of life on the drug just wasn't worth the small dose. It also sounds like you are very athletic and engage in intense exercise frequently which also parallels my life as I have always kept myself in great physical shape. Its interesting how different we all respond to the various MPN drugs. I'm hoping that if I do eventually go on Besremi, I will respond somewhat better than Pegasy's in regards to symptoms. I've never had mental health issues so the bouts of depression were horrible! Your comments give me hope that Besremi symptoms might be less severe. Thank you again and best wishes to you. Kerry
Your improved result on mental health is good news. Besremi does not claim to be better there, but they do claim to be better in general and your experience points that way in many ways.
On the stomach aches, I get some too after the shot. I tried the leg injection site once and it seemed better. It's harder to see what you're doing there, but I will try it again.
You are the first person taking Besremi that mentioned migraines. I've had them all my life, but they went off the rails about 3 months after I started Besremi. And, they had changed: no warning signs, and the frequency increased as well as streaks...3-4 day in a row.
Hunter suggested CGRP inhibitors and that has made all the difference in the world. I believe the initial study showed 39% of those in the trial got headaches, but I don't usually get headaches--I get migraines.
Not sure what you are using, but I suggested you check about Nurtec and AIMOVIG. I use both monthly and take Nurtec if I feel a migraine coming on.
I have ET and I take 50 mcg every 3 weeks. All numbers under control.
That is very low, even lower than Orangeboykitty above at the 3 week schedule and way less than the lowest in the trial. How were your numbers before any treatment?
I see you were on PEG before. Did you get CHR also on a low dose of PEG? Any difference in the experience vs Bes?
Platelets we’re over a million when ET was discovered in 2019. I was put on Hydrea (which brought my platelets, RBC, WBC down close to normal range) for a year, then I transitioned to Pegasys for a little over a year, then transitioned to Besremi at beginning on this year (2022). I got to CHR when on Pegasys but have maintained to date with transition to Besremi. All transitions were driven by me and not my doctor. Learned from Hunter to be aggressive to get what you want!
That is a great result. Did you ever get an allele burden (AB) test? Are you Jak2?
Yes, Im JAK2 and I’ve had 2 bone marrow biopsies which only one was done correctly. Can’t seem to find test at the moment but I want to say it said 6 or 6%. Did it to get a baseline. Will retest this year to see if AB has dropped any. My biggest struggles are low back pain (arthritis), tinnitus, and the fatigue. Thanks for the insightful research, appreciate your posts!
6% is a low AB. Could be that's why you are seeing such an excellent response, but the data on this relation is not so easily figured. I'm also lowish at ~14-19 and getting good response. I'll try to look over the familiar studies for a fresh take on this correlation.
Even if you don't get more reduction right away, at least Bes should reduce odds of increases.
Did your BMB show any MPN conditions?
Agree on the symptom burden, I do recall from the studies that good CHR does not necessarily correlate to symptoms.
On the arthritis, some members have had joint pain improvements with Curcumin. You can search that on the forum. With Dr informed, it might be worth considering if you've not tried.
I believe the initial concern for my BMB was to see if there was significant scar tissue, however, I was told there wasn’t and that was about it. Yes, I agree while if no reduction in AB, I’d still be happy to see that it hasn’t increased. I did clear the Curcumin with MPN specialist but a few weeks after taking them, I noticed the ringing start in my ears so I discontinued. Could just be a coincidence, but I might try it again to see if it helps with back pain. Here’s what I was taking (2 per day).
That is the brand Hunter has used to effect, and I've been taking 1/day of this one.
Looking into tinnitus and Curc, by coincidence this study comes up
clinicaltrials.gov/ct2/show...
<<This study will assess the effectiveness of highly bioavailable curcumin in suppressing subjective tinnitus>>
It comes up in many other results too, so it might not be the cause of that symptom. It does bring to mind, for the many MPNs suffering tinnitus, maybe it could help.
But if you restart and tinnitus also does, it could be contra for you.
On your BMB there should be a lot of text, if nothing else listing all the conditions they looked for and did not find. You should try to get this for future reference. In a recent thread I've had a good lesson in understanding some of the BMB results.
This formulation works great for me. I am taking 4/day - 2AM/2PM. It makes a huge difference with the osteoarthritis.
I recall you were once on 2/day, is that right?
That is correct. I started there then titrated up based on my response.
I am currently at 350 mcgs every two weeks. Just increased from 300 to 350 because my hct went to 47.5 requiring pb. I am currently still requiring pb about once every ten weeks while we try to get the correct dose. Before Besremi I was requiring pb about once per month and was iron deficient and tired. My doc says he has patients on Besremi who can control hct on 100 mcgs and others that require at least a year on 500 mcgs before they get controlled hct. He doesn’t know why and there doesn’t appear to be a correlation between allele burden or severity of the disease and response to Besremi. Apparently they just don’t know why some respond more positively to lower doses. He basically said give it a year and depending on the labs we may increase the dose again. I definitely feel better on Besremi than with the monthly phlebotomies only and my platelets have gone down from 1500 to 800. White count has decreased some but still in normal range. No liver or kidney problems so far. I started Besremi at 100 mcgs app 6 mos ago.
I see your prior posts on the titration. Time wise you're near where the Ropeg study doses stabilized in the top post chart. Of course that's for reference only, our journeys are all unique.
Your Dr's experience seems closer to what we are seeing here (dose all over the place) than to the high dose weighted results in the trial chart at top. Kseely above has a time adjusted dose of 33mcg, for what must be near a lowest known and way off any result in the study. Does your Dr have many Bes patients so far? I am 1st for mine, but likely he has more now.
I've also seen that symptoms and response seem disconnected, see reply to Kseely above. But I have posted on multiple studies pointing to a relation between CHR and allele response. Allele can respond to any HR but more often when it's at CHR. I think it supports the idea of titration for CHR but not more than required for that.
Those same reports found min correlation between dose and allele reduction, mostly instead the CHR/allele connection.
I’ve just started. 50mcg and my 2 week blood draw is tomorrow. All my blood work was within normal limits when I started but I had stopped taking HU 7 weeks prior to starting Besremi.
This thread is gathering great info. It's no way a randomized controlled study or even scientific, but it is a real world snap shot that is enlightening.
I will create a simple point plot from this small sample so we can see how we compare to the real study. I hope we can get a few more replies for that.
The report in the link at top has this qualifier:
<<Because of formulation changes, the prescribing information for starting dose, titration amounts, and maximum dose of BESREMi differ slightly from those used in the PEGINVERA trial>>
I wonder if they "improved" its formulation enough on the fly, or even under the radar, to cause some of the discrepancy we're seeing (our snap shot being apparently well weighted to lower dosing than the study)
Hi, I have been on Besremi since February of this year. I'm at 150 mg every two weeks. My PLT and WBC are now normal! My HCT has been elusive so I've had two phlebotomies and do believe I'll need more to keep HCT below 42. My HEM suggested we slowly increase my dose to 200 only for better HCT control.
When I raised it up last does to 160 I had more fatigue and some weird pain in one toe that was persistent so I moved back down to 150. My HEM believes that higher doses could bring more complications and toxicity, so I doubt he'll ever suggested I increase the dose much more.
My specialist also wants to get to 200, but in my case there is no clear reason for doing so. I'm also at 6 months and feel my max without trouble is 100-120.
Do you feel the phlebs may be able to get less frequent?
Perhaps. I'll know more tomorrow when I have a CBC.
Have you received your latest CBC? In the point plot of the other thread, I put your response in the No-CHR. But actually if you're in range on PLT and WBC and under HCT 45, that is CHR by the rules of the Ropeg study.
I didn't get my CBC...I'll do it tomorrow. Yes, per the study that would be CHR as I don't think the had ideal HCT for women at 42. Thank you for putting this all together.
Thanks. So I'll await your latest but seems we will likely be ok calling it CHR per that study.
Hi there. After 8 months and a current dose of 155ish, my HCT is 41, WBC 6.8. and PLT are 362-the lowest they have been since my dx.
After four doses (100, 150, 200, 200), I’m not yet at CHR. HCT is within normal range, PLT is trending down, and WBC seems to be creeping down. PLT and WBC are still higher than normal. It’s very early, but things seem to be moving in the right direction.
Dr said CHR could take a year. I’m tolerating Bes well so far, and he plans to keep increasing the dose. My fifth dose (injected after labs) was 250, and he wants me to go to 300 next time. I feel some fatigue (not bad) and have had a couple instances of mild nausea (easily controlled with Zofran).
My allele burden is very high, which scares the heck out of me. My last BMB also showed enough fibrosis that Dr took some time to rule out transformation to MF before we started Bes. That was ruled out, but I’m highly motivated to make Bes work in hopes of slowing/stopping disease progression.
Good update on your CBC. HCT can be sticky as we've seen here so that is good progress. If you're already heading the right way, does Dr want to make it go faster with the increasing dose? Is there concern your WBC won't normalize on 250?
I agree starting Bes was a good move. Is your Dr planning an allele test after about a year?
I think he figures we should keep increasing as long as I’m tolerating it well. Then we can adjust as needed based on the counts. He did say yesterday that he’d test the allele after a year.
Thanks for your awesome input and information on this site. I’ve learned a lot from you and others, too.
Currently at 50mg every three weeks. HCT and PLT at CHR. Having trouble with my low Neutrophils, last time they dropped below 1k 🙄
That is a great response, same as Kseely above. I see you're a long timer at more than 1 years, so the longer dosing is consistent, but the low dose is nice.
Were you on PEG before. If so did that work well too?
Do you have an Exon 12 allele % (AB)?
Per the study criteria, you're in CHR since they didn't look for min WBCs.
But as in posts, Neut does need a min more than does Lymph. Does your Dr feel you have margin for even more dose reductions?
I will add your point to the ongoing point plot.
Hello EPguy, thanks for your reply and all the work you are doing here. I haven't been on PEG before, started with Besremi right after having been diagnosed with PV in January 2021, though it took some time to convince my Doc.
I'm currently at the hospital, due to a brain surgery (possible low grade glioma), no results do far.
My leucocytes have dropped to 2.6 l, which really scared 😨 me. Don't have any current values at hands. My Exon 12 burden was 20% at the time of the bone marrow biopsy. It's difficult to get an update for that value here in Germany, as soon as I have any updates on that I will let you know.
Hi EPguy,
I'm now up to 500 mcg every 2 weeks, but have not seen CHR as yet- in fact, since I made the last step up from 450 mcg to 500 mcg, my Hct has gone up from 48, to 50 after the 1st 500 mcg dose, and after the 2nd 500 mcg dose it was 51.
Patience is a virtue they say- but I do get weary of waiting...
Thanks for all that you do here for all of us!
Best regards ,
PA
PS: My pharmacy is Onco360.
Increased Besremi Dose to Be Studied for Polycythemia Vera Treatment
2nd Dose of Besremi Today
Two Besremi doses and the itching begins!!
