Interferon alpha

[Carlalawoo]

I got diagnosed with ET Jak2 positive back in November and 42 years old. I've had my latest blood results back and my platlets are just under 600. Having read a number of posts, this seems quite low compared to others. My doctor has suggested putting me on Interferon Alpha and sent me the leaflet guide from MPN voice. The side affects seem vast and in all honesty, quite scary. The 2 mentioned are Pegasys and Besremi and was hoping someone on the same could explain the benefits they believe they get versus the side affects (I understand the affects will vary from person to person). Just feeling a little freaked out by it all to be honest and looking for a little more info from people in the know. Thanks for taking the time to read x

[hunter5582]

You are asking an excellent question regarding treatment for ET. The first step would be to discuss with your MPN care team why cytoreduction would be indicated in your case. You are correct to think that your level of thrombocytosis is relatively low. People with ET age 42 in the absence of risk factors would be considered low-risk. The usual protocol is aspirin and monitor.

If for some reason (e.g., thrombotic incident, co-occurring medical issues) cytoreduction is indicated, then there are two first-line choices, hydroxycarbamide and a pegylated interferon. A pegylated interferon would be the usual first choice for someone your age. This is related to the long-term risks associated with hydroxycarbamide as well as the risks for people of childbearing years.

You are correct that we all respond differently to the medications used to treat MPNs. Each one of the medications comes with a risk/benefit profile. Even the low-dose aspirin has potential adverse effects. We need to make our decisions based on an objective evaluation of both the benefits and the risks of each choice. To do this, we need to be clear about both our treatment goals and risk tolerance.

I have been on all three of the drugs, hydroxycarbamide (hydroxyurea), Pegasys peginterferon alpha 2a) and Besremi (ropeginterferon alpha 2b). I was refractory to and intolerant of hydroxycarbamide. I responded much better to the interferons both in terms of efficacy and tolerance. The adverse effects I experienced with the IFNs include: itching/rashes that are well controlled by cetirizine, elevation in liver function tests which is well controlled by milk thistle extract, and mild lymphopenia/borderline neutropenia. The IFNs have been very effective at low doses for reaching my hematologic target. In addition, my quality of life has improved due to this course of treatment.

My response to IFN treatment does not predict yours. You will have to decide for yourself whether the benefits of IFN treatment outweigh the risks. If you decide to proceed with cytoreduction using an IFN, it will likely be Pegasys. Besremi is approved for PV but not for ET. Pegasys, while off-label for MPNs, has been in common use to treat ET/PV for decades. Pegasys is also considerable less expensive than Besremi; therefore, it is easier to get approved.

Wishing you all the best moving forward.

[Carlalawoo in reply to hunter5582]

Thank you for taking the time to respond and to tell your story.I'm currently on a baby aspirin a day, drugs for high cholesterol and blood pressure. I also have sleep apnea and finally diabetes.

I'm making changes to my life choices in regards to food, exercise and my mental health. I was hoping this will help and just got a little taken back with the possibility of taking another drug.

Best wishes to you too

[PhysAssist in reply to Carlalawoo]

Hi Carlalawoo,

What Hunter says is true, but there is also some point to starting treatment with an interferon early in the course of the MPN disease process- with the point of preventing progression and even potentially getting to remission- but as he says, it depends on what your goals are, and how you want to live your life.

From my personal experiences, it seems like sometimes you can't adequately tell how bad your quality of life is until you improve it.

E.G., I was just reminiscing w/ SWMBO over the past weekend after working [pretty strenuously] raking and generally cleaning up the winter debris from our yard and garden beds,, that prior to my PV diagnosis [Dx] [and especially my treatment [Tx] w/ Besremi], I would not have been able to work on my feet for the 6 hours straight as I did that day.

Typically, I'd have been out of breath, and my legs and joints would have been too tired, heavy, and sore to keep going.

That's no longer the case- even though I still have pretty extensive venous insufficiency in my legs, they don't really bother me like they used to any more.

I thought that the fatigue and pain were all my normal and to be expected from the consequences of aging and having a lot of arthritis, joint injuries, and vein problems- turns out that I was wrong.

I was sore with some joint and muscle aches that night, and some bit into the next day, but it faded quickly and prior to my Dx and Tx, I would have been totally miserable, although I wouldn't have accomplished nearly as much.

The side-effects that they advertise can happen, but don't be too off-put by reading them- a lot of us either only have them transiently or minimally, and then there's always the possibility of hanging to the next/other flavor of INF.

Best,

PA

[monarch5000]

IMHO you are lucky in two ways; a) were diagnosed early while your platelet count is still only moderately elevated b) are being seen by a competent and caring doctor who is offering you interferon (e.g. Pegasys) immunotherapy at a very early stage of ET disease which is when only low doses that usually have mild or no side effects are very likely to not only normalize the platelet count but also greatly slow or stop disease progression toward post ET myelofibrosis as you get into your 50's and 60's.

There is even roughly a 30% chance interferon could induce a state of Minimal Residual Disease where the Jak2 mutation is nearly undetectable and you would need only a small monthly "disease maintenance" dose to maintain your MRD status for decades.

In a retrospective study of 348 young adults (age < 25) with ET & PV disease, who were followed for up to 20 years, NONE of those who received interferon as a first line treatment progressed to myelofibosis whereas 25% of those who used other treatments did progress within that 20 year period: ash.confex.com/ash/2023/web...

[Carlalawoo in reply to monarch5000]

Thank you for this information, it's very helpful. I found out last week that my grandfather (who passed away before I was born) actually had the PV version, which surprised me, as I was told its not genetic.

I have an excellent doctor and count myself lucky after reading some other people's journeys.

Wishing you the best and thanks again.

[Fivecatsandcounting in reply to Carlalawoo]

My nephew has ET .. diagnosed at age 14 when he was extremely poorly. Platelets 4000 ish and a clot on his liver. Was a bit touch and go for a while I think. Once he was treated initially (Mayo clinic USA) he now has interferon weekly and is doing really well. Age 22 now. I have PV. So we are opposites to you and your grandad :-).

[KyleeR in reply to monarch5000]

This is a great reply! I’m also a 40 year old woman who has just started on Pegasus and the thought that it could slow or halt progression is what I’m holding onto.

I started off at the lowest dose for 2 months before an increase and I found the side effects minimal. Lots of water, fresh air walks and sleep I believe helped a lot. My inbox is open if you need 😊

[PhysAssist in reply to monarch5000]

Totally excellent summary!

[Solebury]

Hi, I hear you in regard to your concern with side effects. I’m 69, have the JAK2 mutation and have had ET (14yrs) which morphed into PV (2yrs). I took hydrea for most of that time but was eventually unable to handle the side effects from that toxic drug. I have been on peginterferon for almost 2 yrs now and I feel pretty good by comparison. Virtually no side effects other than pruritus(itching likely from disease progression) and the normal fatigue associated with a chronic disease. I also now take Jakafi which has helped immensely with the pruritis and has lowered my platelet counts to below 450 for the first time since my initial diagnosis. Good luck, it can be a long winding road and sometimes you just need to take a chance.

[Carlalawoo in reply to Solebury]

Thank you for replying.

I will be speaking to my doctor again regarding the information he sent in the post but wanted to hear other people's stance on the subject. My doctor is very good and said there's no rush but wanted to give me all the options.

It's all a little scary and it helps hearing other people's journey, so thanks again

[Fivecatsandcounting]

Hi Carlalawoo I am on Interferon and have been since last September. I was 59 at diagnosis and 60 now so it was a good choice for me. I was started on 90mcg and inject every Sunday evening. I have PV so high platelets and reds. My platelets were around 1300 and still around 1100 so I'm not sure if it is working well or not. I was increased to 135mcg a couple of months ago to try and improve the counts but I struggled to tolerate that dose and couldn't really function with the side effects. I took myself back down to 90mcg a couple of weeks ago and feel much better. Side effects kick in almost immediately but I go to bed. Slight headache, then dizzy, really fatigued and achy bones and joints mainly but there isn't a strict pattern to that so it could be the disease itself. I'm going to Guys next week so looking forward to what they say. The injection itself is a lot better than you think and very quick and easy to do. I love that it's once a week. I also love that it can reduce the mutation long term. I hope that you get on ok with it. It does seem to Settle. I think I am just a slow responder but know I will get there!

[Carlalawoo in reply to Fivecatsandcounting]

Thank you for responding and good luck for your appointment at Guys.

Do you still take daily aspirin along with the injections?

[Fivecatsandcounting in reply to Carlalawoo]

Thank you yes I do. I think it makes platelets less 'sticky'. I hope that you can get your head around it all. I'm only getting there now and keep notes and records of all my tests and questions. Mpn voice is an amazing resource.

[Carlalawoo in reply to Fivecatsandcounting]

It is weird to get your head around. Still very up and down about it to be honest. Definitely helps talking to others in the same situation and have found MPN voice a real help.

My partner is worried that theirs a lot of misinformation around and i could get caught down all sorts of rabbit holes. But it's just other people's journeys and opinions.

I have started sending myself notes on my phone for questions for the doctor too

[PhysAssist in reply to Fivecatsandcounting]

Exactly correct- it's not a "blood thinner" exactly, but it decreases platelets' propensity to clump together, thus decreasing the likelihood of clotting when not needed. Twice daily seems to be necessary to keep the treatment working [references upon request].

Best,

PA

[DottyDaisy]

Hi Carla. I really wouldn't advise anybody to listen to my advice. I'm a complete rebel and never take anything unless I feel I absolutely have to. That's why, at 81½ and with platelets around 900 I think, I take nothing apart from Vitamic C most days and occasionally D3, B12 and vegan Omega 3 if I think of any of them. Otherwise, I just accept that I often get weak, weary and wobbly and still go off in my micro campervan at the slightest excuse. That and organic vegetable gardening are what fuel my soul and fill me with joy, peace and contentment.

[Carlalawoo in reply to DottyDaisy]

Aww, you sound like you have a great setup and enjoying life.

That makes me smile and gives me great hope, thank you.

P.s I love my caravan too and would love to start foraging and understand the natural alternatives to help

[GardNerd]

The comments of Monarch5000 really resonated for me. I've been on Besremi for almost two years, and I was highly motivated by the potential for it to modify disease progression and possibly prevent transformation to MF.

Like you, I was young when diagnosed. I was 44 when diagnosed with PV. Even after Pegasys was being used to treat PV, my doctor didn't put me on it or even suggest it. I rolled along for 16 years with aspirin and phlebotomies -- and the disease progressed. Then I started Besremi; and, so far, the disease has not progressed further. I would give a lot to go back in time and get on an interferon to potentially modify/slow disease progression at an earlier point.

The side effects freaked me out, too; but I haven't had any troublesome issues. I did experience some melancholy (the mood issues) for a few months, but that resolved. I had some minor rashes, but nothing bad. You never know, since everyone reacts differently; but it's definitely worth a try, and you can always stop it if it's not tolerable. For me, the potential benefits were too great not to give the interferons a go.

Best of luck to you!

[Carlalawoo in reply to GardNerd]

Thank you for replying and telling me about your journey.

I found out last week that my grandfather (who passed away before I was born) actually had the PV version, which surprised me, as I was told its not genetic. He passed away at 54 from a blood clot but I didn't know about his condition.

I will be speaking to my doctor again before making the decision. Its good to hear how others feel about it and I'm feeling a lot better about the situation, so thanks again.

[Wyebird]

peg has given me my life back. Yes it takes a while to get used to it but boy is it worth it. When you first take it it’s like have a bout of flu. Just be prepared take yourself off to bed with paracetamol and ride it out it will take a few days to go away. Every time I took a jab the symptoms got less. After about 5 months no symptoms at all.

[Exeter21]

The things you read are a minefield of How to put you off BUT all drug companies do same. Peg has been brilliant & like you I was put off by reading 🙈. But also read lots of research on it by MPN work & results. I started on 45 weekly 2 years ago but soon changed to 45 monthly . My fitness is good & no side effects. I did however get headaches on 45 weekly but my MPN reverted to monthly & perfect.

All bloods in range again . ET Jak2.

Julia . UK

[Anag]

I started Besremi 1,5 years ago. I’ve ET CALR. HU caused me extreme Nervous system problems and anagrelide cause me increasing heart problems after 5,5 years alternative INFalpha

I started on a dose of 50mcg then 75. After It started working slowly then when I reached 200mcg my thrombocytes plummeted to 250!! First time in 15 years! All the while still taking one capsule of anagrelide. (Earlier 4-6 daily).

Problem. Once the Besremi really kicked in, I stated having pain in my feet, hands, shoulders. Everywhere where I’d had accidents in the past. It got worse with every injection. Diagnosis, brain stem inflammation. I start the treatment for 2 1/2 months. The thrombocytes went up very slowly over 2.5 months. And I started with 50 µg increasing to 75. All was well. Thrombocytes went a bit more down. I increase to 100 µg and pain symptoms started again. In a week I will be reducing to 75. Then blood test.

The good thing about the interference is that it could eventually lead to remission. At the moment, it is the only treatment that actually works on the megakaryocytes and not just the thrombocytes.

Especially for someone, your reaches is the best treatment the earlier you start the better. This is the opinion of my MPN specialist here in Austria.

Pegasys apparently has more side-effects than Besremi. Many colleagues here tolerate Besremi and Pegasys really well. Everyone is different and will have different needs. I will definitely try it. I find it extremely important to start and remain on a very strict autoimmune paleo or low inflammation diet, and to really clean the body of all chemicals and metals. This will give your best chances of tolerating treatments. Make sure you do a lot of liver detox. Keep fit. 🙂

Hope to have helped Anag