JAK+ ET longevity

[Plate]

I was diagnosed ~2.5 months ago. Will this disease ever go away on it’s own?

Will I always be on medication?

Does anyone know the longevity of this disease?

Thank you friends

[hunter5582]

The answer today may not be the same as the answer in the not-too-distant future. There are some very interesting things happening in the research.

The answer today is that there is no cure for the JAK2+ ET. It can be successfully managed and with proper management, people with ET can be expected to live a normal lifespan. It may mean being on cytoreductive medication for the rest of your life at this point in time.

The good news is that options are expanding. We currently have two primary choices for treating ET - hydroxyurea and Pegasys. Anagrelide and Jakafi are second-line treatment options. Besremi and bomedemstat are in clinical trials for ET. There are other options working their way through research as well.

One of the very interesting items mentioned from the most recent ASH conference is a suggestion that it may be possible to find a way to target the JAK2 mutated hematopoietic stem cells. This is quite a ways off, but is something that would be very promising if it moves forward. There is something promising underway with research into a vaccine-based approach to treating CALR+ ET since these cells can be targeted.

There are hopeful options on the horizon. Meanwhile, we have the means to manage ET successfully for many of those with the condition.

Wishing you all the best.

[Plate in reply to hunter5582]

Thank you once again Hunter for your informative reply.

Wishing you the best as well!

[Handysmurf in reply to hunter5582]

Hunter,

Although not directly germane to this conversation can you enlarge on "There is something promising underway with research into a vaccine-based approach to treating CALR+ ET since these cells can be targeted."

Regards,

Ed

[hunter5582 in reply to Handysmurf]

I have not looked extensively into the topic of CALR-ET, but have heard several references to the potential new treatment in MPN trainings. The short version is that the CALR mutation in a hematopoietic stem cell causes a detectable difference in the cell. This would allow the cell to be targeted by something like a vaccine based treatment. There is a new clinical trial underway.

clinicaltrials.gov/ct2/show...

There is information about this in the literature. Here are a few samples.

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

link.springer.com/article/1...

cancertherapyadvisor.com/ho...

This is very exciting news for people managing the CALR mutation. Certainly something worth learning more about. This treatment could lead the way in a new mechanism to treat MPNs. Perhaps, it will someday have bearing for other types of driver mutation as well.

If you are interested in learning more, this is worth learning more about. Please let us know what you learn if you pursue this as we would all benefit.

[Plate in reply to hunter5582]

Thanks Hunter!

[Handysmurf in reply to hunter5582]

Definitely - thanks for the heads up.

[monarch5000]

The disease will never go away completely, but there's about a 30% chance your ET could reverted back to a stage referred to as "Minimal Residual Disease" using the drug Pegasys interferon. If MRD was achieved you would only need to take a disease maintenance dose of the drug (a self administered injection like insulin) about once a month to maintain your MRD status.

Only a small % of hematologists in the USA have experience prescribing Pegasys interferon, or have a favorable attitude about it, so if you are interested in being considered for a prescription you would likely have to travel to see a known interferon friendly specialist.

If you are currently taking hydroxyurea, that drug does not slow or stop disease progression towards post ET myelofibrosis, but on the other hand, some cases of ET do not progress to post ET myelofibrosis for 20-30 years whereas others do in 2-5 years.

In Denmark the leading specialist there has been an outspoken fan of interferon for 13 years as you can see from what he wrote below back in 2014:

[Plate in reply to monarch5000]

Thank you!

[katiewalsh]

Hi. The answers you received may overwhelm you. Trust me that you will adjust to the situation & may not even be troubled by it. Whenever you have questions, fears or frustration you can get great support here. It’s not uncommon for newly diagnosed patients to get upset so don’t feel bad if you do. Remember we’re here to support you and help you on this journey we all share. Take care & be gentle with yourself. Katie

[Ratton]

I felt as yourself when first diagnosed 3 yrs ago- (after just being' cured' of colon cancer

imagine how I felt)???!! Just carry on with life as usual I am now 78 and don't think too much about ET (I am also Jak 2)-take Anagrelide x 2 daily and aspirin and my platelets on last recording were 360-am now waiting to hear results of blood taken last week)

[Jennytheb]

Hi, sorry to hear your diagnosis but I think some things have even changed since I was also diagnosed 7 years ago now.

I was told then that I could only expect a lifespan of 15 years, I have gone 7 of those but now, as the ever helpful Hunter says it looks like a normal lifespan.

I am on Hydroxy as I call it and also take Clopidogrel as I was intolerant to Aspirin mix with Hydroxy and can, as I have often mentioned on this site, say that although my dosage of Hydroxy is now 3 capsules daily, live a lifestyle which is totally unaffected by the medication.

I hope you can get along with the meds and, although it was a huge shock when I was first diagnosed, get along in life as I am.

Wishing you the very best,

Jenny.

[J-fd]

it’s not curable I’m afraid

[lizzziep]

It’s a life long not life limiting disease. I have far more trouble with my arthritis than the ET. Hope all goes well for you. 😊

[Plate in reply to lizzziep]

Thank you! Best wishes to you!

[MissPenguin]

As I understand it, as a newly diagnosed JAK2 patient, there is no cure. We take oral chemo and aspirin for life.

[Exeter21]

please don’t worry as so much to help manage this . I am a year on from the shock diagnosis after a sport injury & blood checks discovered it. Happy it did. I am now monthly dose of Peg Interferon & feeling good . However took a year to get correct doseage. Our bodies all different. Mine did not cope with HU . Peg Interferon had to be experimented as weekly dose gave me migraines but monthly don’t know I have taken it. You will be fine as we have arrived at our journey in MPN great research times 👍. Julia. Devon UK 👍

[ainslie]

I think it’s fair to say most with ET will have a normal lifespan, it’s not curable YET but your just beginning and meds are improving and ET is the tamest of the MPN’s so a lot to be positive about.

[KLCTJC]

My MD Anderson doctor has told me from day one. I will live a normal lifespan. I was scared I would die in 10 years with PV. I am 3 years in and now on Besremi and I feel great. Was odd in the last 2 weeks I magically noticed this difference after being on the medication 2 months. But I feel like my old self, if I can even remember what that felt like! But the world leading expert has always reassured me. And then am also so happy I am treating it! Makes me feel better than just aspirin and phlebotomy, like I am moving in a positive direction. And like Hunter said give it a few years something else will come out. JAK inhibitors and other drugs that block those inflammatory markers are exploding in all areas of medicine. Just a matter of time before something very specific comes out to target these cells. Hope this makes you feel better.

[Plate in reply to KLCTJC]

Are you living in Texas? I am about 75 miles from MD Anderson.

[monarch5000 in reply to Plate]

The video below shows that for ET patients, MD Anderson's docs don't consider interferon superior to hydroxyurea. So if you were to go to MD Anderson with the hope of being seriously considered for a prescription for Pegasys interferon you'd likely end up being disappointed.

Why is it important for a 71 year old ET patient to consider taking interferon instead of hydroxyurea? Because only interferon offers them a chance to avoid disease progression to post ET myelofibrosis. Why is it important to avoid disease progression to post ET myelofibrosis? Because the only way a post ET myelofibrosis can avoid early death is by having a stem cell transplant and post ET patients in their 70's are usually considered too old to undergo a stem cell transplant: youtu.be/VP_eFY8wrlM(Not working as expected?)

[EPguy in reply to monarch5000]

He seems to rely on the study his institution did:

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

Based on the plots, IFN provided no advantage in transformation, and for ET no VAF improvement.

But in the Euro based Ropeg study for Besremi(but only for PV):

"Survival in the absence of disease progression or thromboembolic events was also significantly higher in the ropeginterferon group" (3x difference)

ashpublications.org/ashclin...

Both studies are large and for a long time.

The large cohort with ET in the MDA study might account for the less satisfying result. It seems ET might be less responsive to IFN, same is a trend for Rux possibly. There will be a good quality second opinion with the ongoing SURPASS ET trial for Bes.

Both studies have average allele increasing on IFN after 5 years but still quite good.

--

Recent data in Rux studies found a clear connection of VAF reduction to lower progression. This may also be showing in the Ropeg study.

MDA IFN-ET

[monarch5000 in reply to EPguy]

You've seen this video before where Dr. Kiladjian talks about the differences between his PVN1 study France and the MD Anderson study in Texas.

He notes the MD Anderson patients were older and inherently sicker at the time they started the Pegasys interferon trial and so it's no great surprise they fared worse. youtu.be/vuhwGEi4Y_k(Not working as expected?)

[EPguy in reply to monarch5000]

It does make clear the benefit of starting early, as the Silver group has long said. He noted that MDA was handicapped by both pt condition and their resistance to HU. Inclusion of ET in MDA may account for some of the difference also as he implied and we see in the plots above.

Rux studies to date have also been limited to HU resistant/intolerant. The ongoing Ruxobeat trial does not have this handicap.

[Jamesxyz in reply to KLCTJC]

Just curious, when did you start besremi and were you previously on hydrea?

Thanks

[KLCTJC in reply to Jamesxyz]

Started in February. It is the only medicine I have tried.

[Jamesxyz in reply to KLCTJC]

Hi, Thanks for your reply. Any side effects from the besremi ?

[KLCTJC in reply to Jamesxyz]

not anything that has bothered me. I am just now dealing with a weird period! May not have anything to do with Besremi, but who knows. But overall I feel good!

[KLCTJC]

I do. I live like 3 hours from there. It is worth going. It is an all day deal, but they make sure if you need anything they do it same day. I always bring something to do. But it is 100% worth it. Unfortunately my doctor retired in February but will see a new one that he recommended at my follow up. I also have a local oncologist. They work together. My local oncologist is very receptive and grateful for their help. We do nothing without my MD Anderson doctor being on board.

[Plate in reply to KLCTJC]

Thank you for responding!