How long for Besremi to work?

[SouthSideA]

I've recently started Besremi for treatment for PV. I will be transitioning from hydroxyurea, and wonder if others have experience with this. How long did it take after beginning Besremi for your blood counts to reach desired levels? How were the side-effects? Please let me know, and thanks for any replies.

[EPguy]

Is your Dr planning to stop the HU at once? Normally there is a transition period where HU is decreased and IFN (Besremi) is slowly (and preferably, carefully) increased. Are your counts currently too high on HU?

[SouthSideA in reply to EPguy]

Thanks for the reply! Yes, I gather this is the plan: to decrease HU and to increase IFN and carefully watch my counts along the way. I'm just wondering about how long this might take. I gather that Besremi can take a year or more to effectively address counts, which I think means that I would be on both for many months? To answer your other question, my counts are very good on HU, but I've asked my Doc to allow us to experiment with the switch to Besremi because, at 43 years-old, the potential disease modifying impacts of IFN are compelling. Again, thanks for any thoughts you might have.

[EPguy in reply to SouthSideA]

I've been on HU, IFN, and Rux.

When I reduced the HU and increased the Bes, my counts didn't change. My switch was in the middle of this plot. I show PLT since this has been my main problem on counts.

It could be if one has good control and tolerance on HU this would be a typical experience.

As discussed in another recent thread, there is now compelling evidence that reducing the mutation is effective. So your choice is good. Also good that you will be cautious in your IFN dosing.

Others will let you their sides. I had malaise and then a rare extreme bad reaction. Has your Dr asked about any autoimmune history?

HU to IFN

[SouthSideA]

Good to know. Sorry if I missed this, but how long did it take for the IFN to bring your counts where your Doc wanted them?

I’ll try and find the thread you reference about reducing the mutation. Can you point me in the right direction to find that thread?

My Doc has talked to me about autoimmune history.

[EPguy in reply to SouthSideA]

Here is the current thread. There are others but this has the most up to date on this forum:

healthunlocked.com/mpnvoice...

Sorry for incomplete info. I had zero days to get to good counts since it was good on HU and stayed the same on Bes. That's the green dots that are the same result even as I switched. I transitioned over about three weeks. It's quite possible you will see a similar result.

Good your Dr discussed autoimmunity. I assume you have no troubles there. Not all Drs ask, I care a lot about it now.

[EPguy in reply to SouthSideA]

I edited the plot image to make more clear.

[PhysAssist in reply to SouthSideA]

Hi SSA,

My transition was smooth and I titrated up pretty quickly w/ minimal evidence of side-effects, but unfortunately, although my platelet and WBC counts responded [both were previously quite elevated] my Hct has been less reliably controlled.

There's also this new thread:

healthunlocked.com/mpnvoice...

Best,

PA

[SouthSideA in reply to PhysAssist]

Thanks so much for this helpful reply!

[SouthSideA]

Super helpful. Thanks for the thoughtful response. My doc, who is an MPN expert, says the relationship between JAK2 burden and long-term treatment efficacy is not well established and therefore he’s not inclined to measure it. Still I’m glad to be able to try Besremi in hopes that I’m on the right side of the science, even if it takes years for that evidence to emerge. Does that make sense to you?

[EPguy in reply to SouthSideA]

Ask most on this forum following the issue and the answer will be it has emerged and the past couple years become established. But practice in any field lags info. Of course nothing in medicine is 100% ever, there are plenty of exceptions. I'm one extreme example.

This VAF reduction benefit is not unique to Besremi or IFN, as you can see on that other thread, any treatment that gets the mutation down shares this benefit, right now that is IFN or Jakafi for longer term.

My MPN expert considered it worth following and I believe overdid my dose for that reason.

But your Dr's view is does not make sense, even assuming VAF level is of uncertain use now, anyone can figure that it could be worth knowing in the future. For this you need a starting value for "just in case I wished I knew".

[SouthSideA in reply to EPguy]

I think I’m following you. The bottom line is that my decision to switch to Besremi, assuming it effectively controls my counts, is a wise one, even if we don’t yet know exactly how or to what extent it benefits me. Correct?

Again, I’m grateful for your thoughtful replies, and I’m so glad the drug is work well for you.

[EPguy in reply to SouthSideA]

If counts alone are the goal, HU is a good choice, for example compared to phlebotomies. But your thought is right, assuming there can be longer term benefits, Bes is a preferred option.

But when you asked about side effects, IFN is the only one in our set that has an FDA black box warning. This is for rare but severe, and even more rarely permanent, adverse events. This is why I asked whether your Dr discussed existing autoimmune conditions.

Unfortunately for me, I got boxed by the worst of that black box, you can read in this post. So I'm on Rux now. More typically your Dr will be watching your liver and kidney counts closely.

healthunlocked.com/mpnvoice...

[DougyW in reply to SouthSideA]

See my post of 5 minutes ago about a change of approach in the UK. The probable correlation is becoming clearer with every study into it b

[WYLDEMANSWOMAN]

Hi,51F with PV (Jak2) diagnosed June 2022. Had 2 therapeutic phelbotomies that summer and was started on HU (500 mg daily) September 2022.

March 2023 another phelbotomy and an increase to HU (2 Days @ 1000; 5 Days @ 500).

My counts were under control, but symtpoms (fatigue, brain fog /confusion, headaches, burning eyes with blurry vision, shortness of breath, tinnitus, dizziness and nausea) were still a huge problem. My local hematologist/oncologist worked together with my MPN Specialist (2 hours away) and increased HU again (4 days @ 1000 mg; 3 Days @ 500 mg) for 2. 5 months. No impact on symptoms, counts were still good.

We started Besremi 5/16/2024 @ 50mcg - decreased HU to 2 Days @ 1000; 5 Days @ 500.

5/30/2024 - Besremi @ 100mcg - HU to 5 Days @ 500.

6/13/2024 - Besremi @ 150mcg - HU to 500mg every other day.

6/27/2024 - Besremi @ 200mcg - completely stopping HU.

The plan is to continue increasing Besremi 50mcg every 2 weeks, as long as blood work looks good (liver, kidney, hct, etc), or my symptoms magically disappear (been fighting the symptoms since May 2019. Have gone through so much testing because no one thinks these symptoms are due to PV). SO-MUCH-FUN 😀

Anyway, hope this long winded response helps. Be well.

[SouthSideA in reply to WYLDEMANSWOMAN]

This helps - thank you. It sounds like you’ve made the switch from HU to Besremi over 6 weeks, tapering down on HU and up on Besremi and monitoring your counts along the way. It also sounds like your counts now look fine at 200mcg per injection but you’ll keep increasing by 50mcg. Is that all correct?

[WYLDEMANSWOMAN in reply to SouthSideA]

Yes, correct we will increase 50mcg every 2 weeks as long as there are no adverse reactions and I still have symptoms. Both Dr's have been very up front saying that they are not sure besremi will eliminate the symtpoms, but they are willing to try it. I am game too, considering quality of life is almost nil. Would like to get some assembliance of my life back.

[KLCTJC]

I have been on Besremi almost a year and a half and I guess you would say I am in a sort of remission. My wbcs and platelets fell immediately and like everyone else HCT lagged behind. Had one phlebotomy 3 mos after starting then at the 6 mo mark we hit a steady state. We did the low slow approach and I landed at 225mcg until this last month. Now I have responded so well we are backing off. Hct is now 38! It did push me thyroid over the edge which I always had subclinical hypothyroidism but on levothyroxine and that is all good. Other than that no side effects and I feel great!!! To me it has truly been a miracle drug sent from god! Everyone is different but for me it has been life changing in so many ways. I feel like I have my life back and I could live to see my grandchildren one day, which is all of our goals!😊. Good luck wish you the best!!

[SouthSideA in reply to KLCTJC]

Thanks so much for this encouraging report. I'm so very glad you've had such a positive experience with Besremi. Keep going! You got this!

[KLCTJC in reply to SouthSideA]

BTW I am 42, saw you are young as well. I really hope it works as well for you as it has for me. I have kept a positive attitude through the treatment and felt in my gut it was going to work. Not sure if I willed it to work or what! But it has saved me and my family. Will be praying for you!!! If you have any questions you can always reach out! Have a great weekend!

[SouthSideA in reply to KLCTJC]

This means a huge amount to me. Thank you. I don't know if this is appropriate, but if you're ever open to connect directly, I would welcome that. Having a younger person who is going through this and with whom I can communicate would also mean a lot. May I share my cell?

[CLake4]

I am wondering the same thing! However I never started HU and started Besremi in February 2024 on the "Eclipse" trial. I started at 100mcg and after 10 doses am now at 500mcg. My white counts are now in normal range. My platlett s are now half (was over 1mllion and now 688 k/uL) but my Hematocrit consistently moves above target of 45% resulting in 4 phlebotomies since February which is a lot for me! I am told that my JAK2 cells are fighting back and at the high dose Hematocrit should finally respond. Yesterday I took my second 500mcg so hoping this month I finally get good numbers. I know everyone says low and slow is good.. but sure would like to stop those phlebotomies! The significant side affect I have experienced is neuralgia in my feet. The nerve pain is really bad at night and at the high dose I could not sleep and had impact at work. So this week I started taking Gabapentin at 300 mg at night only. Has anyone else taking this drug? It's side effects sound as bad as Besremi so hoping for the best. Am I the only one that was slow to respond to Besremi?

[EPguy in reply to CLake4]

Severe ongoing neuralgia that emerges with IFN therapy is not normal. It can be a sign of developing autoimmune disease. IFN has this rare but potentially permanent risk as described in its FDA black box warning.

I suffered nerve pain from an adverse vaccine reaction while on Bes. It morphed into an evil autoimmune disease, see my post Last Dose. Odds are you're not headed this way but your risk may be elevated if neuralgia is presenting. You want to be sure this risk stays near zero. You should discuss this with your Drs and a rheumatologist right away.

I also took Gabapentin for a while after the vax injury, but am now intolerant to it.

[CLake4 in reply to EPguy]

Thankyou. Will definetly discuss with my PV md. She was not at my last appointment so will definetly discuss.

[PhysAssist in reply to CLake4]

Hi CLake4,

See my post below, and my other posts re: my experiences w/ Besremi.

Our response pictures are mirrors even though I've been on Besremi a lot longer.

My Hct was 50% last week, after close to a year at 500 mcg/2 weeks.- but my WBC and Platelets have responded [almost too] well and are low normal routinely.

I have never had any major side-effects or problems, just not enough Hct control- although to be fair, my Hct and RBC counts were massively higher beforehand. [like 60's or Hct % and 700's for RBC's.]

I'm significantly less concerned about thrombosis [clots] than when my WBC were 15K along with the ^^^Hct and RBC's, though.

My main reasons to go on an IFN were disease progression, coupled with untenable HU side-effects.

Best,

PA

[hunter5582]

The how long question varies between each individual and with the dosing approach you choose to use. The recommendation from PharmaEssentia in transitioning from HU to Besremi is to start at 50mcg and increase in 50mcg every two weeks until hematologic target are met. While increasing the dose of Besrem the dose of HU is gradually reduced. There are a number of individual patient factors that determine the titration schedule. The goal is to switch as quickly as possible providing that the dosing change is tolerated and hematologic targets are met within the expected timeframe. The norm is to do labs every two weeks until hematologic stability is established.

One of the factors to be considered is your preferred treatment strategy. Not all doctors or patients choose the rapid dosing increase of Besremi. Many prefer the "low and slow" approach. I would fall into the latter category as I prefer a more conservative dosing strategy and was will to be patient in waiting for the response. Note that I was switching from Pegasys to Besremi when I made the switch. I had discontinued the HU over a year earlier as I was refractory to and intolerant of the HU. I chose to increase the Besremi dose in 25mcg increments, which my MPN care team was fine with.

The side effects from Besremi have been much easier to tolerate than HU or phlebotomy-induced iron deficiency. I have experience itching and occasional rashes. The skin issues are well controlled with a daily dose of Zyrtec. I experienced an increase in LFTs to 3x/upper limit of normal. A daily dose of milk thistle extract returned the LFTs to normal. I also experience mild lymphopenia and borderline neutropenia. We have set keeping LYMPH>0.50 and NEUT>1.00 as the target. This has kept my max dose of Besremi at 175mcg as it does impact my leukocytes. Fortunately, the 175mcg is an effective dose for me. I am maintaining a complete hematologic response, but do seem to need a phlebotomy about once per year. This does cause the problems that regular phlebotomies used to cause. My allele burden has dropped from 38% to 10%. Note I am in the camp that believes that this does matter.

The most important thing of all is that I feel better on bersemi than I did before starting it. It is more effective and easier to tolerate than any other treatment I have tried. I feel better now than I did 10 years ago. Quality of life matters more than any other treatment goal.

Wishing you success with your treatment strategy.

[SouthSideA in reply to hunter5582]

Thank you for this thoughtful, encouraging response. Do you or others have thoughts on how we (those of us on Besremi) evaluate whether, in fact, the medication is actually slowing the course of the disease? Measuring allele burden is one possible way, but the connection between those two values is unclear. Perhaps, the science just needs to advance?

[monarch5000 in reply to SouthSideA]

We can't answer your progression questions without knowing what your blood counts were before having any phebotomies or starting hydroxy, what they are now. And we would need to know the general, summarized findings of your bone marrow biopsy report, if you had one.

[hunter5582 in reply to SouthSideA]

My own thoughts on preventing progression of the MPN breaks down into the definition of progression. There are different aspects of disease progression.

1. Progression into MF/AML. Monitored in part by following CBCs over time. BMB is certainly more definitive but not something we would repeat unless there was a compelling reason to do so. I do believe that VAF is a valid biomarker regarding progression, but it a correlation not an absolute marker. The significance of VAF should become more clear as the science develops.

2. Spleen size is an important marker. While not as common, liver enlargement is also important to stay aware of. This is a reflection of extramedullary hematopoiesis.

3. Other MPN symptom increase is another marker of progression. Changes in issues like fatigue, pruritis, erythromelalgia, headaches, dizziness, tinnitus, etc, all matter and reflect the status of the MPN.

I would note that my primary treatment goal is to maintain a high quality of life. There is no other goal, including extending length of life, that is as important. Not to say say that extending length of life does not matter; however living well is more important than living long for me. How I think about measuring progression reflects my goal structure. Others may look at measuring progression differently.

Wishing you all the best on your journey.

[GardNerd]

I was on phlebotomy only until starting Besremi in June 2022. The platelets and other aspects of the blood responded quickly, but it took almost 11 months for the hematocrit to be under control. As I adjusted to the Besremi, I felt some mild fatigue, some moodiness (which thankfully went away), and minor rashes. Two years in, the only side effect for me is the periodic rash and dry skin here and there.

I think you’re being very wise and proactive to go on an interferon at your age. I was diagnosed at age 44 and didn’t start the interferon until I was 60. I was fine on phlebotomies and living life fully. Little did I know, I was giving the disease every opportunity to progress silently during those years, and it did. Luckily, I had not progressed to MF; and the Besremi is working very well. If I could do one thing differently over these past 18 years, it would be to get on an interferon as soon as one was available.

I also believe the allele burden matters, and you may have the opportunity to keep that low from the start. Like EPGuy said, it would be worth it to know what your allele burden is — just one more bit of information. It can be counted through blood work (a BMB isn’t necessary to get that info). My doctor told me just yesterday that the interferon does most of its allele burden reducing work in the first three years. After that, the interferon keeps it down. Of course, data is still developing here. Nonetheless, it would be nice to know where you are at the beginning of the treatment.

Best of luck to you!!

[SouthSideA in reply to GardNerd]

Very helpful. Thank you! I’m 43 and was diagnosed a few months ago. Starting interferon early is good advice, and I’m taking it. I’ll also ask to measure my allele burden so we know where I am at the beginning of the treatment. Again, thank you for the sound, thoughtful reply.

[CLake4 in reply to GardNerd]

May I ask what dosage of Besremi you were on to get the Hematocrit under control?

[SouthSideA in reply to CLake4]

I think your question is for another person above, correct? Perhaps GardNerd?