How effective is Hydrea in stopping progression to myleofibrosis

[TrailCookies]

I was on Hydrea but suffered extreme fatigue. Now I am on Jakafi and have numerous side effects (stomach pain, diarrhea, fatigue). When I was on Hydrea my blood counts were normal. Which drug will keep my counts stable for the longest period of time?

[hunter5582]

Of the three main treatment options for PV, the current evidence suggests that Besremi is the most likely to be disease modifying, with progression free survival. There is emerging evidence (reduction in JAK VAF) and reason to be hopeful that Jakafi may also have this benefit. Hydroxyurea can be effective for controlling blood cell counts but will not do anything to prevent progression. HU is not disease modifying.

All three medications can be effective in long term stabilization of the blood cell counts; however, we each respond differently to each of these medications. Some find one effective but not another. Some are able to tolerate one but not another. I was refractory to and intolerant of hydroxyurea. I have responded much better to Beremi both in terms of efficacy and side effects. Moreover, my JAK2 VAF has reduced from 38% to 10%. Of equal importance, I feel better now than before I started on Besremi. In fact, I feel better now than I did 10 years ago.

Please note that we all react to these medications differently. My response does not predict yours. We each have to determine what our treatment goals will be as well as what our risk tolerance is. All of these medications come with benefits and potential adverse effects. We each need to determine which option aligns best with our own treatment preferences.

Wishing you all the best.

[TrailCookies in reply to hunter5582]

Thank you for sharing your experience and excellent advice and understanding of the MPN medications. I will have labs in two weeks, so then I’ll see what effect Jakafi has on my blood counts. Also, thanks to you I have more information and questions to discuss with my oncologist.

All the best to you!

[Loubprv Volunteer in reply to TrailCookies]

HmmmI was on HU for 15 years then came off it due to skin probs

Am now on Rux which seems fine.

Tried peg interferon which put me in hospital for 4 days and attacked my auto immune system.

My haematologist says Besremi doesn't suit everyone either and didn't think it would be a good idea for me.

I think it's a matter of trying to find the best drug to suit you, but we have to bear in mind that these are manufactured chemicals we're either swallowing or injecting and so sadly, may have side effects of some sort

Are you sure the fatigue is from Rux and not your mpn?

Silly question - Are you drinking at least 2 litres water a day? That can make a massive difference believe it or not.

Hope you feel better soon

Louise

[saltmarsh in reply to Loubprv]

You are sooo right. Thanks for the post

[Scottishterrier]

Hi was diagnosed with et jak2+ in 1994 I had high platelets but in 1999 I was after a trip to the states I started what I thought was heartburn and was chewing gaviscon for fun my parents and two work colleagues were saying I was yellow and not eating so I told haematologist consultant who ordered CT scan in November and spoilt my Christmas and new year and as soon festive period was over got on to my doctor who wanted to see me I had a clot on liver got appointment with my consultant and put on hydrea high dose to start yes it makes me feel tired but got my platelets down to near normal and I am down to one on a Monday but I am still under constant supervision from consultant bloods done six weeks before appointment at GP and again at my haematologist appointment Stay safe

Scottish terrier

[TrailCookies in reply to Scottishterrier]

Thanks so much for sharing. Scary to have a blood clot on your liver; thankfully the Hydrea helped you. I wish you continued good health!

[Meatloaf9 in reply to TrailCookies]

Hi TrailCookies, You have asked a great question, have you also considered the interferons? What is your diagnosis and age? I have been trying to get a direct answer to that question from my MPN specialist and other specialists on webinars to tell me if I should switch from HU to besremi for 2 years now. I am 75 with PV on Hu for about 4 years now and blood counts are perfectly controlled and I have no symptoms or side effects that I know of right now from the HU. I asked my specialist to make the decision on meds for me, he would not. He did say "why mess with success". I sort of think that making my own decision on my treatment of blood cancer would be like being your own attorney in a murder trial, you know what they say about that. In December he told me that you can stay on HU for a very very long time without problems, his words. Of course if we do progress to MF there is no going back as far as I know. It seems to me that I have read of quite a few patients on this forum that have progressed to MF while taking interferons and the possible adverse reactions to interferons seem to possibly be more severe and possibly permanent, think autoimmune. This is simply my experience, not any kind of advice. Best to you in finding the answer to your question, please let us know your decision. Best always.

[TrailCookies in reply to Meatloaf9]

Hi Meatloaf9! I am 75 years old also. My diagnosis is “pre-fibrotic MF” or “early post-ET myelofibrosis.” I have progressed past ET but am not yet in MF. My question about how to stop the progression to MF weighs on me. I have the JAK2 mutation as well as a ASXL1 mutation which is a higher risk mutation.

Thanks to everyone for offering their diagnoses and treatment experiences. I have much to discuss with my MPN oncologist.

Best to you!

[EPguy]

One way to think of it is any drug that you cannot tolerate will be unable to hold counts long term no matter how well it works. As you found, HU did a good job but it can't hold your counts because you don't tolerate it.

I got good counts on all three, HU, IFN and Rux. But I felt not too good on HU and IFN ended with a bang. For all of them, the smallest dose that works is more likely to enable long term use. What dose did you have on HU and have on Rux now?

If your doses have been the lowest required for good control, then IFN is worth discussing with your Dr as a 3rd option. Like IFN, Rux can take a while to get best blood response so you may not find it at the next draw. IFN also is not tolerated well by a signif patient portion so it calls for careful attention while on therapy.

As Hunter says, IFN is well known to reduce the Jak2 mutation for many, and Rux is lately known to do the same. Both can also modify the disease course for many.

[Richinspirit]

No drug can stop progression to Myelofibrosis., they simply control and moderate symptoms.

[ainslie in reply to Richinspirit]

So far we don’t know that , ie no drug can stop or slow progression, maybe maybe not

[EPguy in reply to Richinspirit]

There are two separate reports for Rux I've posted on in a few places, this is one of the familiar plots in a 12 year study. They were prospective with progression as a study endpoint, for HU intolerant pts ( a tough audience) . They found the mutation can go down (all the red bars in Fig. A, for MR, molecular response) with Rux, as it does with IFN, and having an MR leads to reduced MF progression. Not responding (no MR) conversely correlated negative outcomes. IFN has similar progression benefit in retrospective studies.

The zero progression line was up to 2% mutation I recall.

Having certain non-Jak2 mutations has an influence on the response.

rux pv

[Richinspirit in reply to EPguy]

what a fabulous well informed comment - thank you!

[DELLAZ in reply to EPguy]

How do they test progression of Jak2- through blood draws or bone marrow?

[EPguy in reply to DELLAZ]

It can be both. At Dx patients often get a bone marrow (BMB) and a jak2 measurement is usually included. But to watch for changes over the years, blood is more practical. So getting a blood reading near the same time as the BMB is useful for future comparisons. BMB and blood do not necessarily give the same number, mine were quite different.

[DELLAZ in reply to EPguy]

Thanx

[ainslie]

you have had some great answers already but no one knows which drug will keep your counts stable for the longest time. Rux can for some lower AB which is quite likely a good thing which may help keep counts under control more easily and possibly the disease better controlled than Hydroxy which usually only lowers AB temporarily, Hydroxy has a good history for counts control but has no possibility of slowing progression. If after a while you can’t tolerate Rux then Peg/Bes is worth a try, it can also for a subset lower AB and maybe maybe slow progression. As EP Guy already mentioned Rux can take a little time to have full effect so maybe dont conclude after the first blood test. Typical start dose is 10 mg am and 10 mg 12 hours later, 10% need less than start dose but 60% need more, I am on 22.5+20 for PV.

[monarch5000]

Depends on your doctor and country. In Denmark, interferon was favored to slow or stop progression to myelofibrosis back in 2011-2014 area and still is today (see below). The Danes consider interferon the best drug for thwarting progression, Hydrea ineffective and Jakafi in-between the two.

.

[monarch5000]

Jakafi has only been available for about 12 years so there are no 20+ year long studies comparing it to hydroxyurea and interferon, but there is this retrospective study that looked at how well interferon prevented progression of ET and PV to myelofibrosis over a 20 year period vs hydroxyurea:

.

[Meatloaf9 in reply to monarch5000]

Thank you for posting this, could you tell me what year this was published at the ASH meeting? Best to you.

[monarch5000 in reply to Meatloaf9]

2023: ashpublications.org/blood/a...

Note the Conclusion: "These results support the use of IFN as a currently available disease-modifying agent to improve Myelofibrosis Free Survival and also warrant reconsideration of earlier treatment in patients with ET and PV with IFN to improve Myelofibrosis Free Survival potentially as a primary aim.

[monarch5000]

Some MPN specialists who prescribe alot of the Pegasys brand of interferon have reported a alot of their patients feel better: Brief example: youtu.be/OsdoYoA1kLQ(Not working as expected?)

[Cja1956]

I’ve been on Hydroxyurea on and off for years. I’ve also been on Jakafi at different times over the past 16 years. The thing with these medications is that they eventually stop working. When my ET morphed into MF in 2019 my doctor changed from jakafi back to hydroxyurea because my hemoglobin was dropping and my platelet count was rising. But by 2021 I was getting bad side effects like shortness of breath, mouth, sores, night sweats, and increasing fatigue. In June 2023 I became pre-transplant and my new doctor put me back on jakafi. It has changed my life and I was able to put off the transplant for almost 2 years. All of my symptoms went away . I’m going into transplant in May this year. So I guess what I’m trying to say is that everything is a balancing act and that’s why they monitor us so closely.

[Artjoy]

My blood counts tended to be low on Jakafi, but my quality of life improved: more energy. We are all so different in our responses to drugs I do find that all our drugs have G. I. side effects. I took Aranesp injections occasionally to raise my hemoglobin while I was on Jakafi. I stayed on Jakafi longer than most—10 years, at which point it stopped controlling my spleen size. Ojjaara completely normalized my counts, but I felt noticeably worse for the 10 months I was on it—I caught every conceivable bacterial infection and felt sick all the time. I never had a stomachache while on Jakafi, but occasionally do now because my enlarged spleen is pushing against my stomach (clearly evident on a CT scan of my abdomen). Now I am on a clinical trial, feeling better, but still fatigue. Good luck with whatever drug you’re next—they are all a crap shoot.