Besremi dose 2 is today. Things are actually looking pretty good and I will be sticking with the 100mcg dose for now. While my HCT is at 45% we are not going to change the dose. The concern is that with LYMPH low and NEUT borderline, we do not want to further suppress leukocytes.
I copied my patient portal correspondence with my wonderful MPN Specialist at Johns Hopkins, Dr. Braunstein. This is an example of what quality MPN care looks like. Note that Dr. B typically responds within 24 hours.
Sent this note to the MPN Specialist
CBC today 02/14/22
HCT down a bit 45.0% from 45.2% 1/31.
WBC up to 3.38 from 2.94
NEUT up to 1.92 from 1.38
LYMPH down a bit 0.80 from 0.82
No side effects to report from the Besremi other than lymphopenia, which was already present on Pegasys.
I am thinking the jump in HCT from Dec 10 from 43.3 is likely due to iron levels getting higher and driving up the erythropoiesis. Your thoughts?
We adjusted the start dose of Besremi to 100mcg since HCT was above 45%. It nudged down in the right direction. Do you recommend keeping dose at 100mcg?
If we bump the dose up, 125mcg or 150mcg? Note that I would prefer a bump up in dose to having a phlebotomy. I feel better with iron levels higher.
Dr. Braunstein's response
I agree with your assessment. It seems you don't really need a hematologist anymore...
I would stick with 100mcg for at least a month or two and see how your blood counts respond before increasing. Higher doses are likely cause more leukopenia. I have seen this with Pegasys, so will be important to monitor. However from a molecular response standpoint, there is evidence that higher doses are better.
I don't think you need phlebotomy for HCT slightly above 45 as long as you continue on the Besremi.
My response
LOL! I am pretty sure I still need a hematologist (or two). I have a whole bunch of other "ologists" too. Will stick with the 100mcg as recommended.
FYI - I decided that with HCT up a bit I would up the aspirin from 40.5mg qd to 40.5mg bid. Seem to be tolerating it OK. No sign of the excessive hemorrhage I saw before on 81mg. Maybe having platelets around 400 is better than closer to 800 when you tend to be a little bleedy/bruisy.
Thanks
I am very fortunate to have two great hematologists on my care team, the MPN Specialist and a great local hematologist who handles my ongoing care needs. Both docs treat patients with compassion and respect. I always get two opinions on all MPN care decisions. It is a terrific care team.
All the best to all of you all (properly pronounced all y'all).
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hunter5582
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Hello,I think you are fine with 100mcg. According on my hema, Dr Spevak, Besremi is long acting drug, then we have to be patient and slowly it works better.
You dont drink coffee because it can slow the absortion of the Besremi doses because it stop the gene called CYP1A2 and more. We need it fine.
Here are the references regarding the impact of interferons from the link. "Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients;... and reduce metabolism via CYP1A2 (caffeine).
It would appear the IFN may reduce the clearance of caffeine from your body.
I believe SoledadBarecelona's comment is related to this consideration.
Additional Considerations
ropeginterferon alfa-2b in Besremi
caution advised w/ narrow therapeutic index drugs; interferons may suppress CYP450 enzyme activity, resulting in incr. exposure of CYP substrates
epocrates
Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body.[5] In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.[6]
WIKI
The CYP1A2 enzyme is responsible for 90% of caffeine metabolism, and for 84%, 12%, and 4% of the metabolism of caffeine's metabolites: paraxanthine, theophylline, and theobromine, respectively16. A SNP in the CYP1A2 enzyme (−163C > A; rs762551) has been suggested to influence the inducibility of CYP1A2 activity.
Nature.com
My limited understanding of the above is that Besremi and caffeine are both metabolized in the liver and involve CYP450.
ePocrates does not note a drug interaction. I did find this on Drugs.com for Pegasys. I expect Besremi will be the same.
CAFFEINE ORAL AND PEGINTERFERON ALFA-2A SUBQ
caffeine oral will increase the level or effect of peginterferon alfa-2a subq by altering drug metabolism.
I think this would indicate that caffeine may slow the breakdown of Besremi.
If it increases the peak values that would be a negative, since BES is specifically for leveling those. But as you say if it smoothly extends it, that is good.
In this study, for hi doses of non-peg INF, there are some other foods they were instructed to avoid:
<<All of the subjects were instructed to abstain from alcohol, caffeine, barbecued meat, and grapefruit or grapefruit juice consumption for at least 2 days before each visit>>
I know grapefruit is relevant to statins or the like but this introduces a larger idea of whether there is a list of foods relevant to INF that we need to know about.
--
In this summary INF affects caffeine clearance, but no mention of the other direction, caff effect on INF clearance.
I did see reference to IFN affecting caffeine, but not the other way around.
My assumption is that it is like most things, moderation is the best approach. I stick to one cup of caffeine/day anyway due to the arrhythmia. I think I will just stick to that plan.
Too much fruits and weets are no good to microbiote which control our immune system. Remember that Besremi is a stronger immodulator. It was said by Aaron Logan at ASH21
Agree too much sugar is bad, esp as concentrated in sweets. My recent Glucose is lowest ever, possibly affected by my NAC supplement. I plan to post on that in the future.
You say "Besremi is a stronger immodulator" Can you provide the link for Aaron Logan so we can understand this better, for example better than what? It sounds important.
Hunter,Thank you so much for your posts …… they are SO helpful to this learning process on blood numbers …… Im on Pegasys now for 3 months, presently 90mcg per wk.
Good progress. Your Drs comment "However from a molecular response standpoint, there is evidence that higher doses are better. " matches what I've been figuring.
Esp with the better tolerated INFs I think the goal is to get the highest possible dose that is tolerated. My Dr indicated the same. This is different from HU for example that gets just the dose that gives specific measured results.
At a certain level that would be common sense. It is always a balancing act. Besremi may be easier to tolerate but still can have significant adverse effects. I do want to be careful about dropping my LYMPH and NEUT any lower than they are now. Providing I keep the erythrocytosis under control (HCT<45%) I will stick with the lower dose. It does also have the platelets WNL, but I really am not as concerned with that provided it does not get too high.
Agree on keeping the overall CBC values WNL. Would you call that part of the tolerance equation? Could be you have already found your stable dose, but I think they want a year to better set it.
It is all a balancing act factoring in erythrocytes, leukocytes and platelets. The IFNs can decrease all types of blood cells. Need to keep the erythrocytosis under control without inducing too much leukopenia. Given that 45mcg of Pegasys has been my stable dose, 100mcg of Besremi may well be the same. We will see what happens over time.
Hi Hunter, at this stage of your treatment, how often do you have a CBC and do you have any other regularly scheduled blood tests, CMP? Thanks for sharing.
Since I just shifted to Besremi, I am doing a CBC every 2 weeks. We will do that until we are sure that we have the dose correct. The CMP will also be every two weeks at first. Over time we will back off on the frequency.
Interesting....I just did my third dose of Besremi, and 50mcg is keeping my hematocrit at just over 42 and platelets in the 300's. So for me the lowest dose of PV meds seems to keep my numbers in check but if there's a side effect to be had, I'll have it. From Besremi I'm slightly dizzy. My hematologist noticed I was speaking more slowly than usual (granted I was speaking Hebrew!) and my face was slightly puffy. Hopefully those things will go away in time and no need to increase my dose. I have to go back in 4 weeks for a BMB, which I will be having this time with sedation.
Great news! Not wishing to steal your thunder, I was also delighted with a call from my consultant yesterday. She hadn’t forgotten what I’d said about statin use - I cited the Dec ‘21 article by Drs Hasselbalch and Silver that EPGuy shared - and when I told her I’d forward it, she gave me her email address, which has since enabled her to send me a blood test form and confirm appointments. All this followed several hours of hanging on to phone lines and being redirected by endless switchboards whilst listening to computerised muzak, simply in a bid to order more Pegasys. If anything she reads about the potential synergistic effect of statins and Interferons (by reducing circulating inflammatory cytokines, etc.) proves useful for a single patient, then this will have been another good outcome of this forum. People have helped me here; I’d be delighted if, as a result, I might be able to benefit others in turn by sharing journal articles. Sharing is caring. Oh, and I administered my 7th dose yesterday: all fine, and she thinks I’ll stay on 45mcg and drop the HU in 12 days’ time. 🤗
That is great news! Physicians who listen to patients and treat them with respect are the very best type of physician. You are another case-in-point that educated and assertive patients receive higher quality care. Passive patients do not.
Thanks. I took your lead and realised that paternalistic relationships in medical settings are not always helpful. It’s not easy for people to change ways of thinking or to become more assertive when they’re naturally more passive, but it’s clearly beneficial for patients and their treating physicians alike. 🤗
Have you considered a short term light dose of hydroxyurea in addition to the besremi to get your HCT back down. I am on 90 mcg of Pegasys weekly but my HCT got above 45% one week and just one HU every other day knocked my HCT back down to 43% after just three doses. I tolerate both drugs well and they have different methods of reducing RBC production. Its part of my treatment plan.
I am hydroxyurea-intolerant. I experience toxicity even at very low doses. I would opt to either increase the dose of Besremi or seek a different adjunctive treatment. If I could access Rusfertide, that would be my first choice. I could consider Jakafi, but need to be careful about further reducing leukocytes. That is what Rusfertide would be a better choice. hopefully it will make it through clinical trials and become an option for all of us.
Hi, Hunter, great news on the Besremi. I really chuckled at the comments from your hematologist. He was closer to the truth than you think. You really seem to know more about Mpns than a lot of doctors. I hope you continue to improve.
That is really a scary thought! Alas there is some truth to it. I often have to explain what PV is and how it can impact you to doctors. I recently had a orthopedist (who is a great doc) ask "What is Polycythemia Vera? It has been a long time since medical school." He listened to the explanation and about the role that systemic inflammation plays. We ended up with a great treatment plan for a knee injury that prevented the need for surgery. It really does work better when doctors respect patients and listen to them.
HunterThank you for the great post! Sounds like you have a very solid plan and support from your doctors. Very interested in the caffeine and inf potential interactions as I love my coffee!
Great news,Hunter! You are so lucky to have such good rapport with your Haematologists. I’m certain that if you show some knowledge about your condition and bloods they do treat you with more respect and listen to your views accordingly. I agree with your Specialist at Johns Hopkins your knowledge is fantastic and has helped lots of us here. Kind regards , Fran
Coffee? So what does coffee to do with interferons? Also what about Statins. Dr Silver awhile ago said everyone should be taking statins with an MPN because it reduces inflammation.
Quick question. Self administering my first Besremi dose tomorrow with nurse online to guide me. What is the best location for injection based on your experience so far. They have given me stomach or thigh as options if I do it myself. Thanks in advance.
I also started the besremi. 1st dose this past Tuesday but I'm tapering up from 50mcg due to tapering down the hydrea. I never had much side effects from pegasys so this felt basically the same except a headache that ibuprofen took care of. I was at the max dose of pegasys and still required hydrea so we will see if besremi works better for me and hopefully off of hydrea! Keep us updated on your progress Hunter!!!
So happy to hear about all the new Besremi users out there. Congratulations and best of health to you all. We are all watching these posts with such excitement and anticipation for each and every one of you.Please continue to post all your good and bad news. We will learn and heal together.
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