I've was diagnosed with Jak2+ ET in March, though the BMB report stated they couldn't exclude pre-fibrotic myelofibrosis as a possible differential. It's been a bit of a crazy ride, but am now under the care of an MPN specialist (what a difference a specialist makes!) My symptoms include fatigue, headaches, dry eyes, vision problems, joint pain & inflammation. My treatment is currently daily aspirin, which has eliminated most of the headaches. My platelets have been on a slow but steady incline since 2016, but have yet to break the 600 threshold.
My Dr thinks I'd qualify for a clinical study on Besremi for ET. I don't think this drug is available in Canada yet, so this may be a unique opportunity. It would also provide an opportunity for me to get tested to determine my allele burden, which isn't a test we readily get in Canada yet (in my province at least.)
I have a pro/con list on the go, and am working on a list of questions to discuss with the research assistant on Monday. I've searched 'besremi' on this forum and have read many of the posts (and will continue to read thru the rest over the weekend, PS: EP Guy, your experience is particularly terrifying!) but I thought it might be helpful to reach out and get some thoughts from those who have walked this path already.
I've gone back and forth a few times on what I should do, so I'm hoping some of you can provide some valuable insight I may not have thought of yet. Part of me worries I'm not "sick enough" to need meds yet and could I be rocking the boat unnecessarily and end up with more symptoms/side effects than I currently have? On the other hand, there are some specialists of the mindset we should be treating these conditions much earlier than typically happens currently to prevent progression and this would be a way for me to be proactive in that sense. I'm an overthinker at the best of times, so my brain is kinda spinning out right now.
Do you have any advice? Things to add to my pro/con list? Questions I should be asking before I commit one way or the other? Experiences you'd like to share, either about Besremi specifically or about clinical trials in general?
Thank you in advance for sharing your thoughts and stories. I'm so grateful for this community and for knowing I'm not alone in this journey. xo
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WRLM
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There is not going to be a black and white answer to your question about whether it is worth it to try Besremi to treat ET at the point you are at. It will depend on what your treatment goals are, what your risk tolerance is, and how you prefer to approach treatment.
From what you describe, you are symptomatic beyond the low-level of thrombocytosis. Are you aiming for better symptom control? Are you going to focus only on preventing thrombosis? Are you hoping to halt the progression of the ET? Do you believe that achieving a molecular reemission is an appropriate goal?
Once you are clear on your treatment goals, what are you willing to risk to achieve those goals? While Besremi has clear benefits, there are also risks to consider. It is important to define what risks you are willing to take and what adverse effects are tolerable.
There are different approaches / philosophies to treatment. Do you prefer a minimalist approach and only want to reduce risk of thrombosis (aspirin-only)? Would you prefer chemotherapy (hydroxyurea), immune modulating therapy (Besremi/Pegasys), kinase, inhibition (Jakafi), or a novel approach like LSD1 inhibition (Bomedemstat)?
Putting all these factors together, you can decide what is in your best interests. I did opt to treat PV (erythrocytosis + thrombocytosis) with Besremi. It was a good choice for me. Besremi has been more effective and much easier to tolerate than hydroxyurea and venesections. I feel better now than i did before I started on besremi. My allele burden has been reduced from 38% to 9% on a low dose (150mcg). Adverse effects have been minimal: mild lymphopenia and borderline neutropenia, mild itching and rashes (controlled by Zyrtec), and elevation in liver enzymes (controlled by Milk Thistle extract).
Others have not had the same experience with Besremi that I have had. That is true for all of our treatment options. We all respond differently. The good news is that most of the time adverse effects will resolve if you discontinue the medication. If you believe that the benefits outweigh the risks then it is worth trying. Trying is the only way to find out. you are the only one who can make the decision since it is your priorities that are the determining factor.
Thank you, Hunter! I was hoping I'd hear from you. 😊
You've done a great job at refocussing me on what my goal is. I like the idea of hopefully halting progression. I know so many talk about how low the risk of progression is, but given how low the risk of getting ET in the first place, those numbers don't provide much peace of mind to me. Better symptom control would be a nice bonus too. I'll reexamine the risks from that perspective and see how things sit with me after that.
There are a ton of preliminary tests that are required before I'd be accepted into the study, many of which haven't been done before, so there may be some peace of mind that comes from a very thorough pre-check, assuming they don't find anything lurking under the surface.
It is quite time consuming to participate, especially since it'll be about a 2hr commute each way, on top of the time required for the actual appointments. That said, I can make it work when so many wouldn't be able to. I do feel some sense of moral obligation to help since I know we wouldn't have the drugs we have now if people weren't willing to participate in these studies, and I know the only way this improves for others in the future is for some of us to help out in this manner (if we can, no judgement to those who can't for whatever reasons.) Yes, I'm also the girl who doesn't try to get out of jury duty because I feel like it's one of those things that needs to be done for the greater good.
I was definitely getting overwhelmed and a little off track with my thought process, so I really appreciate your guidance to help me refocus. I think this will help immensely, so thank you!
Thank you for your kind words. You are most welcome. The process above is how I think about any medical decision. We each always have to weigh our treatment goals, risk tolerance, and treatment preferences. It is both our right and our responsibility to make decisions this way.
Thank you for considering enrolling in the clinical trial. you are correct that this is the only way that treatment science can move forward. It is also the only way new drugs like Besremi can be added to the FDA approved list of medications for a rare disease like ET.
Regarding Pegasys, the approach suggested by monarch5000 is exactly what my daughter (who has JAK2+ ET) was told to do by her hematologist should she wish to pursue Pegasys at some point. This issue here in the USA has to do with insurance formulary requirements. HU and PEG are both off-label for MPNs in the USA but in common use. Some insurance companies require the patient to fail on the cheap drug before allowing access to the more expensive one.
I think its great your doctor is encouraging you to enroll in the Besremi interferon trial, but am a bit puzzled that he apparently did not tell you Pegasys interferon - essentially the same drug - has been available in Canada for more than a decade (although if you're in the province of Ontario he might face difficulties prescribing Pegasys).
Because your platelet count is low, you would likely only need a low dose of Pegasys or Besremi that would likely have minimal, if any side effects. The huge benefit of starting interferon now, in the early disease stage, is that the chances that the drug could induce a durable, potentially life long state of Minimal Residual Disease are greatly increased.
Here's a link where you can read about why, 10 years ago, a veterinarian who had a platelet count just a bit higher than yours, was desperately seeking a prescription for interferon (she abbreviates it as INF) because she was keenly aware it was her only opportunity to have a good chance of avoiding progression to myelofibrosis. imageshack.com/i/pof1VkpNj
My Dr did tell me about Pegasys, but indicated it's only an option if you've failed on HU first. I'm quite nervous about HU because I'm a very pale (bordering on translucent 😜) red head who is very prone to sunburns at the best of times. I love to be outdoors with my dogs, and while I live in a rainforest half the year, we do have amazing spring/summers here and it would really decrease my quality of life to stay indoors, hiding from the sun. I think I'd be very anxious and constantly worried about skin cancer if I were on HU, so my preference is to avoid that path unless it's absolutely necessary.
You're likely correct about possibly needing a low dose, and I'm not sure that would be an option if I were part of this study. There is a dosing schedule laid out and I'm not sure if I could deviate from that, but I've now added it to my list of questions, so thank you for mentioning that.
That article sounds really interesting - I'm just about to dig into it. Thank you for sharing!
One way (in the USA, not sure about Canada) to "fail on HU first." is to try it for 3-4 weeks and then tell your doc you consider the side effects to be intolerable. In my case, I told my doc: "the morning fatigue is so bad I struggle to get out of bed until noon".
That is interesting. My new MPN specialist wants to keep me on hydroxyurea. I have been on it for 13 years and am very concerned about disease progression. I told him I am very fatigued, but that hasn't changed his mind. I often stay in bed until almost noon and spend most of the rest of the day on the couch or lying in bed working on my laptop. If I have to do anything that involves standing, I have to take frequent breaks. He suggested sleep apnea might be the cause of the fatigue. So, my GP is going to have me tested for that.I am in the U. S. and can't afford the $100-$200 per shot copay insurance companies require. So, I guess I am stuck on HU, like it or not.
Yes hydroxyurea causes great fatigue and you're trapped on it unless you can muster the energy and interest to take action on two fronts: 1) make an appointment with an interferon friendly specialist. 2) apply (can be done over the phone) for a grant to cover the cost of the monthly co-payment for Pegasys. We would have to know your geographical location to put you in touch with the nearest interferon friendly specialist.
Hunter and Monarch have both provided valuable and insightful information here. I’ve been on Besremi for 16 months for PV. I’m very glad I went in this direction, mostly motivated by a desire to alter disease progression, reduce the allele burden, and slow/stop the march toward myelofibrosis. So far, so good.
For me, the side effects have been minimal and tolerable. The most troubling side effect was some moodiness/irritability, but that resolved itself after a few months. I moved to the max dose of 500 McL and stayed there for about a year. My platelets got a little low, so now we’re titrating back down to find the dose that will keep things mostly normal.
Like Hunter said, there are so many things to consider that are very personal to you. Knowing then what I know now, I would have given an interferon a try much earlier in the course of my disease.
Good luck! Also, great move to see an MPN specialist.
Hi WRLM, I am so glad that you have the option to take this trial. We in BC do have the option of Pegasys, however Hydroxyurea is the reference drug. That means that to be given Pegasys you must first either fail treatment with HU or be intolerant to its side effects. To be included in this trial you may not have had a previous trial of Pegasys (pegylated interferon or as in the article posted by Monarch, INF).
My experience on Pegasys has been very good. I do have fatigue (not present before treatment) but to balance that I have just been told that after slightly less than 3 years on it my BMB in September shows no evidence of ET (my previous BMB was typical of ET). I am very happy with that and my specialist has determined that with a lasting Complete Haematological response and normal BMB, I can come off of Peg and continue to be monitored. Had I no fatigue I would continue.
As both my father and his brother died of complications of ET and PV, I consider this a win. Even if most people die of something other than their MPN as often quoted. I have the Jak2 defect and have not had a quantitative test (allele burden or VAF) as you have noted it is not available to BC residents.
I was over 60 and my platelet increase was found right away due to blood tests for other reasons. Because of the family history I asked for a haematological consult and pressed for testing of JAK2. The specialist that I see has said that early treatment and early CHR may mean that I have some time to enjoy remission. It is not a cure but I will take it.
Questions to the research assistant I would ask: How will the drug be started (low is better at first to minimize side effects). Of course what side effects are expected and what will signify that Besremi is not the choice for your particular case (in that case when can you stop). How long is the trial and if the trial ends and you are doing well can you still be offered the drug without having to pay for it? Other concerns would be the time commitment for testing. Getting the allele burden is a plus I think as high burden can be indicative of more likelihood of progression which I am sure you know.
So as Hunter and others suggest it is totally up to you and your aims and tolerance.
Best of luck and keep us all informed of your choice and progress.
I was hoping you'd chime in with some advice - thank you for taking the time to help me!
Wow! I'm so thrilled to hear of your success with Pegasys! I truly hope your remission is long lasting (and that the fatigue clears up for you too!) Amazing results! Congratulations!!
I appreciate the questions you've suggested and I've added them to my list.
What I do know is that it's a 1 year study, with an option for it to be extended up to 3 years total if you're benefiting from the drug. I'm not sure what the options are at the end of the 3 years, but I'll ask that question. The titration period is only 4 weeks, and it seems like a high starting dose and a quick ramp up to the full dose (starting dose of 250mcg at week 0, mid-dose of 350mcg at week 2 and a final, target dose of 500mcg and week 4 and onwards.) That is a bit worrisome based on some of the personal experiences I've read. I'm not sure if there is any flexibility with that in terms of increasing slower if needed, or if there's an option to lower the dose if there are any issues along the way. I can excuse myself from the study at any time, for any reason, if I so choose.
The allele burden portion of it is quite interesting to me, but I will ask to be sure that the information will be shared with my Dr & me. There is an additional, optional bone marrow biopsy study and I notice that the results of any testing from that will not be shared with the dr or the patient, so I will be declining that one. I had a pretty bad experience with my first BMB and doing 3 more over the course of a year does not interest me, particularly if the information won't be shared with my Dr. But I will ensure all of the testing results from the Besremi study will be shared with my Dr before I commit.
It is a big time commitment, particularly since I have to add on about 2 hours for commuting back and forth each time. I will need to attend every 2nd week, at least until I'm at the highest dose and stable. At that point they can teach me how to self inject and I can do every other injection myself with a short phone appt and lab visit close to home. So, I'd only have to attend once a month from that point on.
Part of me is fearful of the side effects and possibly feeling worse than I do now, but the idea of watchful waiting has never really sat very well with me either. It seems counterintuitive to just wait for things to get really bad before we try to do something about it. The chance of a CHR without any thrombotic event or waiting to become high risk is obviously very appealing!
Your success has given me so much hope! Thank you again for sharing your success and for your advice as I navigate this decision.
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