Almost 1 yr on Peg - Update

[Solyesh]

Just realized that I started taking Peg in late September 2021...it has been quite a ride. Briefly: diagnosed with ET Jak2+ officially in Dec 2020 via BMB (but had high platelets and leukocytosis for 6-10 years prior to that). Allele burden of 40% (Jak2) and 4% TET2.

Had been on aspirin only and monitoring since 2014 (when my GP got two high platelet readings in a row and prescribed baby aspirin as a preventive measure (but interestingly enough did not refer me to a hematologist - would have to change doctors for that to happen). Even after Dx stayed on aspirin only regime until platelets shot up from about 900 to 1.400 and had bleeding at the gums. MPN specialist suggested, despite relatively young age (52) and no history of thrombosis, we start cytoreductive therapy. As is usually the case for ET, HU was first line medicine offered. Started on HU slowly and eventually worked my way up to 21 pills/week. Was starting to be effective in controlling blood counts but was too toxic for me personally.

Worked with MPN specialist to switch to Peg (which I had been keen on since the start as it seemed to be the only medicine currently out there that can possibly move us toward molecular remission / slow progression (I have always been worried about progression given the attributes of my particular case of ET).

Started at 180mcg/2 weeks. Worked almost immediately to help drop platelets (by about 100 every reading (so every month) and within about 5-6 months platelets were around 600 (our target) and all other readings (particularly WBC) were in line...but then got abnormal liver readings (very elevated AST and ALT although Bilirubin has always remained WNL). Discontinued Peg for 6 weeks - liver readings came back in line but both platelets and WBCs shot up.

Went back on Peg at half the previous dose - so 90cg/2 weeks. Seemed to be working well with blood numbers coming down but still evidencing liver sensitivity (the readings were elevated but not as bad at as at the peak) . At July 2022 reading my MPN specialist stated that "if we could freeze" my results forever we would be happy (platelets at 480; all other bloods WNL however liver still elevated (ALT a little less than 3x top of reference range and AST almost double - these are still much lower than the peak of ALT=4x and AST=3x).

Over this summer, travel and family plans meant I took the Peg (90mcg) every 3 weeks instead of every 2). I could have traveled with the Peg as I had in the past to maintain the every 2 weeks regimen ,but also wanted to see what would happen if we spread out the doses somewhat). So good news is that my liver function is fine on that dosing! AST WNL (at top of range but within) and ALT slightly elevated (very slightly). WBCs still in range as all other blood readings as well EXCEPT platelets jumped back up from 480 to 687...so what to do.

Met with my MPN specialist yesterday - I had suggested either perhaps going for a slightly higher dose (try to get 100 mcg every three weeks) or same 90 mcg at a different interval. After discussing it, we decided to maintain the 90mcg and try it at every 2.5 weeks (so every 17/18 days). We'll see if this maintains my liver in good stead but also brings platelets back down. As my MPN specialist stated: "platelets are important but so is your liver".

I am lucky that I have an MPN specialist that understands my key goals on treatment and QOL and is willing to work with me. Our plan, if the liver stays calm, would be to repeat the allele burden (most likely via BMB again) after being on an effective dose of Peg for a full year.

Happy that Peg works well for me. It had a very significant and almost immediate CHR with few if any side effects (well except for the liver...) - hoping if we can keep the liver in line (btw thyroid was also acting up slightly but was brought immediately into line with medication) then we'll remain on a maintenance dose of Peg for 12 months and re-test to see if there has been any molecular response.

Always reminded of how individual each of our MPN presentations are (as individual as we are) and how much trial and error is involved in trying to hit our individual "sweet spots".

[Aneliv9]

Does your MPN doctor believes ropeg. can take you into remission/ slow progression to MF? Is it really easy to happen? Also did ropeg upset your liver's counts?

[Solyesh in reply to Aneliv9]

My MPN specialist agrees with the current research that as of today, the only available medicine that might (and he always stresses MIGHT) move ET into remission/slow progression are the interferons. The way he explained it to me, backed by info here and my own research, the limited studies to date seem to be most effective for PV but also works for ET. If we can get to a stable dose of Peg for a year we will re-test my allele burden to see if the Peg has been able to reduce it (move toward molecular remission).

Yes, without a doubt, it was the Peg that upset my liver counts. As this is a well known potential side effect, my doctor was running CMP alongside my regular bloodwork and Thyroid readings at every lab visit. So we caught it as soon as it spiked..when I went off of the Peg for 6 weeks my liver counts went back to normal.

We are trying to find the combo of Peg dose/time interval which can keep my platelets under control while not upsetting my liver. The doctor also said that over time he has seen cases where people tend to adapt to the interferons and sometimes things "auto-correct" on their own after a while.

[Hopetohelp]

I see your dose has been every 2 weeks or more. Would it be worth trying a smaller dose, 65 or 45 weekly? I know my body doesn’t like a higher dose but tolerates low regular doses

[Solyesh in reply to Hopetohelp]

Thanks - Interesting as I did query my MPN specialist on that very idea - he said it might work but he would first prefer to try to see if a slightly shorter time frame (2.5 weeks vs 3 weeks) might do the trick on reducing the platelets as we know that my body seems to be able to tolerate (liver) very well when spaced out..if this doesn't work then next step might be to try smaller weekly doses...

[Scaredy_cat]

Your specialist seems a good one. Are you in the UK?

[Solyesh in reply to Scaredy_cat]

I do feel very lucky to have him. No I am in Israel.

[FG251]

Fingers crossed this first course of experimental action works!

My platelets are well under 400 now (322 at last count), where my haem wants them. I’ve tolerated 45mcg/week well since starting PEG in Jan. I’d like to be able to space out the injections at some point - I have yet to have this conversation with my haem - as travelling with the syringe in my medicine cooler was less effective than hoped (it crept up to 6 degrees within only a few hours, but maybe I left the ice block out of the freezer for too long, or maybe I shouldn’t have kept it in the boot of the car, even though it too was in a cool bag?). I see from others’ posts that some are injecting once every three weeks. I wonder at what point that becomes feasible?

[joyfuljoyful123]

Dosage is an art! But pls keep us updated on your journey.

[Jamesxyz]

Hi, Just curious with the liver numbers elevated, did the Dr caution you about any alcohol consumption?

[Solyesh in reply to Jamesxyz]

After the first elevated reading he did caution to limit alcohol consumption as much as possible. I cut it out completely for those 6 weeks. Afterwards he said he didn't think consumption in moderation would make that much of a difference so go ahead and have a couple of glasses of wine a week; etc. To be honest, I feel (and it may be psychological) that my body is not processing alcohol the way it used to. I can't drink more than really half a glass of wine or one hard spirit cocktail so maybe it is naturally limiting?

[Elizka in reply to Solyesh]

I think that happens as we get older. Lots of friends who are not on IFN say the same thing about being able to tolerate alcohol as they get older.

[hunter5582]

It is great that you have a hematologist who is working with you based on your goals and preferences. It sounds like you have a good plan in place. I think you are quite correct abut how we each need to find the sweet spot based on how our individual body reacts.

All the best.

[Jamesxyz]

Hi, Thanks for the info. I'm considering trying besremi,

I usually have a couple of beers before dinner. I have never had any liver issues, but am concerned that IFN might change that.

[Solyesh in reply to Jamesxyz]

Luckily the vast majority have no liver issues on the interferons..so hopefully that will be the case for you too!

[Elizka]

My liver was fine until last week. Not it is mildly inflammated according to my hem. We are monitoring and I didn't drink much to begin with (maybe once a week), but I will eliminated alcohol going forward to see if that helps.