Starting Rux Next Month

[mfh7]

After five years of phlebotomy only with PV I started besremi two years ago at the minimum dose since I wanted to take a more early intervention approach. Also my platelets were extremely high from all of the phlebs. Been on max dose of besremi now for over a year. Besremi lowered my platelets and normalized everything but the red count/hct. Unfortunately lowering the red count is the primary goal and I still have phlebotomy every two months. In that regard besremi has failed as it does for a certain number of users. They don’t know why. Could be secondary mutations is the working theory I think. My MPN has recommended I switch to rux since for whatever reason the interferon is not controlling my hct even after the max dose for over a year and the hct control is the primary goal for my situation.

My question is whether anyone here had no hct control with interferon but had better luck with rux/jakafi in that regard. Also has anyone here had allele burden reduction with rux?

Thanks in advance.

[Ovidess]

I have only taken Besremi, and am now on it at its smallest dose. My platelets came way down from over a million into the normal zone for a while (currently slightly above), and my HCT has pretty much been in the decent zone the whole time, but I notice the red blood cells never get into the normal zone, and the doctor does not even seem to think think that a goal. It makes me wonder if he is focusing on the right thing. When I was first introduced to a diagnosis of ET in 2023, it seemed to be mainly about controlling the platelets, but as I learn more, platelets become less important and stickiness of the blood looms large. I got upped to two 81 mg aspirins a day. Is it true that medicine really has no answer for the sticky blood issue?

[mfh7 in reply to Ovidess]

We are all different but I also had good results in terms of lower platelets from besremi but for what it is worth my mpn doc seems insistent that for me it is the control of the hct i.e that is the most important factor and since besremi has been unable to do that after two years we need to try something else. Fingers crossed the jakafi will work for me and eliminate the need for phlebotomy. Best of luck to you as well!

[jon1972]

I am in the same boat with the ineffective HCT control on IFN. Homozygous for PV is another reason for HCT resistance. Peg sort of helped for a while before becoming ineffective and bad side effects, and I finally had to stop taking it. I recently tried to get put on Jakafai and got denied by insurance since the label says to try hydroxyurea first. So I started taking HU a week ago, but almost hope that i'm intolerant since I have always had a bad feeling about HU. Very toxic with Leukemia and skin cancer risk (according to the label). Good for you for being able to get on Rux/Jakafai. I've been having the same questions you asked.

[mfh7 in reply to jon1972]

Thanks for your reply. Are you in the US? If so I would recommend appealing the decision of your insurance company in denying Jakafi. The insurance companies make their decisions solely based on cost concerns as I’m sure you are aware. My MPN specialist helped me with the appeal and got it done for both besremi and now jakafi. What does Homozygous for PV mean and how do you know it exists for you?

[jon1972 in reply to mfh7]

Actually I'm not certain that I'm homozygous, but on my bone marrow biopsy they said my allele burden was very high, I want to say 60%+. They had a side note saying that this is associated with more aggressive disease characteristics, which is often associated with a homozygous mutation. Homozygous means both alleles on the gene are positive for the mutation instead of just one (heterozygous). Someone can feel free to correct me if my terminology is off with any of this. Under the same insurance I have been previous approved for Pegasys and Besremi, but they didn't like the request for Jakafai. I think it's the most expensive of them all. My doc didn't want to try and fight it saying that given their reasoning that I didn't have much chance of winning an appeal. So I elected to take the route of going on HU first. I'm most likely going to have some side effects that I'll ultimately use in my case for an appeal. But I guess this is the easiest route to get through the appeal process. Yes, I'm in the US and go to Cleveland Clinic.

[Sewingtime in reply to jon1972]

@jon1972 I was started on HU for PV and it got all my blood counts right but did absolutely nothing to help with the itching, which felt like it was taking over my life. My hematologist wrote that I couldn't "tolerate" HU (which wasn't strictly true) and moved me to Jakafi, which my insurance didn't question. Good luck!

[EPguy in reply to mfh7]

jon1972 has it right on the homozy. It's associated with higher mutations since each gene pair has two vs heterozy where only one of the pair is mutated. Homozy also on avg responds better to IFN re allele reductions. It's why we often see members here with dramatic reductions from very high starting values.

Is your Jak2 VAF 40% after two years on IFN? If so that suggests not a lot more to be had and could be another good reason to try Rux.

[EPguy]

I've had good blood counts on HU, IFN and Rux, so not a match there.

But I've also had continuing allele burden (VAF) reduction on Rux as of last. There are other members who have also posted good reductions on Rux, consistent with the trials.

There are regular posts of members here with weak HCT control on IFN, as you refer.

What secondary mutations do you have?

[mfh7 in reply to EPguy]

Asxl but only 10%. 40% jak burden for what that stat is worth. I’m familiar with the references to the possibility of a potentially poorer prognosis with that additional asxl mutation but hoping that doesn’t apply to me. I’m 57 and was diagnosed at age 50. Im having slight spleen enlargement for the first time this year even after two years of high dose besremi so hoping the jakafi will help there. My two primary concerns are hct control and progression. Hoping jakafi will help with both. I tolerated besremi well at max dose for over a year and it was great at lowering platelets but I think the lack of hct control is relevant to the spleen so need to try something new .

[EPguy in reply to mfh7]

I agree, possibilities are not destinies.

Rux is known specifically as being good for spleen reductions for many. If you tolerated Bes that well, is the combo Rux/IFN an option for you?

[mfh7 in reply to EPguy]

Yes spleen is another reason for me to switch to jakafi. They can’t do combo besremi yet since it hasn’t been tested in combo yet. I asked that exact question yesterday since I have read good things about combo therapies. Would have to be combo jakafi peg and I think that is reserved for people that have progressed to mf. Could do combo jakafi and hydroxeria I think but I don’t like what I have read about hydroxeria. Also it would be really hard to get insurance to pay for combi jakafi and peg since both are extremely expensive meds. My insurance company did approve jakafi without an appeal so that was good.

[EPguy in reply to mfh7]

It was tested in the Roxopeg trial, but only for mf as you say. That trial included many with higher risk mutations and should be relevant for the safety results. Very unlikely to ever get FDA approval for the combo in any indication since no one is going to do a ph 3 trial. (unless there is a surprise lurking) But any Dr can Rx any approved drug. I'm probably futility hoping for this approach for my Sjogrens.

But you're right, insurance is the big issue in most countries.

[monarch5000 in reply to mfh7]

The Rux/Pegasys interferon combo has been tried in polycythemia vera (see study below) and some of the interferon experts in the USA and Denmark have experience prescribing it for PV (and also the Besremi + Jakafi combo). It's considered the most advanced treatment available for aggressive cases of PV like yours where the patient still needs regular phlebotomies in spite of taking a high dose of interferon.

The combo is likely to lower your RBC and HCT counts so that phlebotomies are less frequently needed. It should also help lower your mutation allele burden percentages better than interferon alone. And shrink the spleen better. And allow for lower, more easily tolerated doses of interferon to be used.

The key to obtaining the combo is the patient's ability and willingness to travel to one of the handful of specialists who have experience prescribing it and getting insurance approval for it. Like Dr. Gaith Abu-Zeinah in New York City or Dr. Angela Fleishman in Costa Mesa, California weillcornell.org/ghaith-abu...

ncbi.nlm.nih.gov/pmc/articl...

[EPguy in reply to monarch5000]

I found I actually posted on an earlier iteration of this study last year.

healthunlocked.com/mpnvoice...

I've gone thru the one you refer and there are some good fresh points. I have made a new post on it. Thanks for the reference.

[ainslie in reply to mfh7]

Rux plus peg is used for PV also

[ainslie]

first thing is 1 year is not that long for Inf to normalise counts, as previously posted I know of several PV patients that it took 2 years at 180mcg before reds were controlled, one patient is now on 90 and he says Jak2 is undetectable. The fact that Bes controlled your other counts is encouraging and fair chance reds will follow, most experts would likely say same, it may be worth getting a second opinion from a MPN expert.

Re Rux, it may well work in controlling counts and may reduce allele etc, or a combo might work very well.

I am on Rux fo PV and doing well but if it was me and I could tolerate Bes I would give it longer and then if it didn’t work try Rux or a combo but best get a expert opinion.

[mfh7 in reply to ainslie]

Thanks for your reply. probably wasn’t clear on my initial post but I was on besremi for over two years with over a year at the max allowed dose. So we gave it a good try with the understanding it takes a while for hct control. Ultimately there was no improvement in terms of hct control and my mpn recommended hydroxeria or rux. I choose rux and starting it next week. I am getting good advice from my mpn and trust her implicitly, but really just posted on jakafi to get some feedback from other patients in terms of whether it did the trick for them. Combo is not permitted here for besremi and rux together and insurance would not pay for both regardless. Glad to hear you are doing well on rux and wishing you the best.

[ainslie in reply to mfh7]

Rux could well do the job, it did for me, very good for stubborn spleens etc. One point re the combo idea, I asked my expert if I should add Peg to my Rux, he said no because the both do the same job but in different ways. I’m not sure about that but that was what he said.

[EPguy in reply to ainslie]

to ainslie:

"...he said no because the both do the same job but in different ways"

That should be an excellent reason to go for the combo, at reduced dosing for each as the respective trials have done. It would increase odds of deeper benefits. But of course if Rux is working well it makes sense to leave it alone. I have no more option for IFN so it's out for me anyway.

[ainslie in reply to EPguy]

Which are the trials you refer to.

My expert thinks adding Peg would no nothing as Rux is already doing it, I hope he is right, anyway I had major tolerance issues with Peg although Hasselbach would argue that combining Rux with the Peg helps Peg tolerance.

[EPguy in reply to ainslie]

See my fresh post on the subject. You could be a candidate. Hasselbach is an author so his view is consistent.

healthunlocked.com/mpnvoice...

But if Rux is working adding a non-zero risk does need thought.

[Sewingtime]

Hi, I had an allele burden reduction with rux from 60% to 25% in a little less than 2 years. Good luck!

[mfh7 in reply to Sewingtime]

Glad to hear it. How long did it take for you to get hct control with rux. Do you have pv and if so are phlebotomy free at this point? Thanks

[Sewingtime in reply to mfh7]

Yes, I have PV. My hematocrit was already under control with hydrea. My doctor switched me to rux because hydrea brought my blood counts under control but did nothing for the terrible PV itching which was taking over my life! Dosage on rux was a little bit trial and error to start but I have been consistently on 5mg am and 10mg pm for last 18 months or so. My hct, rbc, hemoglobin are all a little on the low side and my rdw and platelets are a little on the high side but we've settled on this as the best of all worlds and I feel great. No phlebotomies since I started on hydrea.

[mfh7 in reply to Sewingtime]

Sounds like you have found the right treatment. Thats awesome. I am so disappointed that interferon didn’t do the trick for me after hearing all of the positive responses, but optimistic that rux might work. I have to say that the besremi did reduce the frequency of phlebotomy from once a month to once every two months and was a miracle in reducing my platelets but ultimately the lack of any significant hct control was a deal breaker for my doc and me after over two years of waiting for it kick in. If rux doesn’t work then I will try hydrea. All the best!

[Sewingtime in reply to mfh7]

I am sure rux will do the trick!