Long Term INF Results: I've posted on other... - MPN Voice

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Long Term INF Results

ETguy profile image

I've posted on other threads about INF treatments. I decided to start a new post since I just came across a most relevant study that should wake up our doctors if they are paying attention. In any other cancer I think this result would be called revolutionary, but since ours is such a slow motion and rare journey, the medical field doesn’t get worked up.

It compares INF (Interferon) , HU (Hydrea) and Phlebotomy for Jak2 PV over a very long time, starting in 1966 to 2019. The triple comparison is neat by itself. It was most recently published this year. In my opinion it should be relevant to the other MPNs since the current standard PEG seems to be effective in many of the things we all care about. But it is specific to “well defined” PV.

The authors are from an institution that was among the earliest to start trying INF.

This study follows the old fashioned rIFNα, not the peg versions, since PEG was not available back then. We can hope that PEG and Ropeg will have at least this or better results since the basic actions are similar but they are easier on the body.

Below is a summary from the report. MFS is myelofibrosis-free survival, OS is overall survival.

-----

-Low Risk- (generally under 60)

--20 year MFS /OS--

INF: 84% / 100%

HU: 65% / 85%

PB: 55% / 80%

-Hi Risk- (Generally over 60)

--20 year MFS /OS--

INF: 89% / 66%

HU: 41% / 40%

PB: 36% / 14%

====

My take is INF is the best way to stay MF free and live singif longer.

This adds to the trend supporting 1st use of INF with hope that Ropeg

will open up the option more more of us. Low risk generally means under

60 years, high risk over 60 or with other risk factors.(prior clots

etc)

At the top is one of several graphs in the report. In the lower set the green and red lines are Phleb and HU. The blue one is INF. Note how much higher the blue lines stay for so many years. The authors are not impressed with long term HU.

If you’re up for it, read the reports, links below, and let us know your thoughts.

onclive.com/view/interferon...

ashpublications.org/blood/a...

Audio from Author:

mpn-hub.com/medical-informa...

29 Replies

Fantastic. I've been thinking a lot about my hematologist's approach to my treatment which is aspirin and watch and wait. Meanwhile, my platelets and WBC continue to go up and I have terrible fatigue. I not only want to get old, but I want to feel better now. Could INF be the answer?

ETguy profile image
ETguy in reply to Lena70

With your treatment your Dr likely put you in the Low Risk category. The info I see all points to starting INF early. The study above covers both Low and High risk patients, you might discuss it with your Dr. Is your HCT ok? I know in PV they monitor HCT especially and your Dr might be waiting for it to go too high first. Problem is the Drs mostly care about your CBC results, not your misery. Hunter has posted his holistic approach and great team.

Among the readers here who can tolerate INF our tiny sample suggests it is very effective at symptoms. My postings are part of my own search to make the INF case soon with my Dr. My prior Hematologist said INF is no better than HU, which is old thinking for old INF that itself is negated by the studies here.

Lena70 profile image
Lena70 in reply to ETguy

Hello. Yes, my hematocrit is at the high end of normal, so fine. I just had bloodwork today. I have high eosinophils, basophils, and platelets. I also have low lymphocytes.

Tomorrow I'm attending a webinar on treatment options that I hope will be enlightening and help me better communicate with my hematologist when I see her in a month.

powerfulpatients.org/event/...

ETguy profile image
ETguy in reply to Lena70

I won't be able to make that webinar. I hope they save it to see later for those who miss it.

I would agree that PEGylated Interferons offer a very promising option for many people with MPNs. I reviewed the studies you cited as well as the other recent research on PEG, which is why I elected to begin treatment with Pegasys. So far I am very pleased. At 45mcg it is having the intended benefit with no adverse effects. While PEG may take longer to be effective than hydroxyurea, I believe the evidence supports its superiority in the long-term.

Hopefully the ropegylated form of IFN will be even better tolerated and widely available soon.

ETguy profile image
ETguy in reply to hunter5582

Do you have more studies we might use for making our case to our Drs? When I showed the Continuation PV allele reductions to my 1st hematologist, he was impressed but it didn't change his attitude about INF.

Here is an excerpt from another study you have likely seen. It makes Ropeg ever more tempting.

"Patient 002 experienced elevated AST/ALT while on PEG, which normalized after four q2 week doses of ROPEG (8 weeks of therapy). Patients 003 and 004 who had persistent fatigue on PEG, saw significant improvement of their symptoms after switching to ROPEG"

ashpublications.org/blood/a...

hunter5582 profile image
hunter5582 in reply to ETguy

I imagine you have seen all the same studies I have. PEGylated Interferon is recognized as one of two first-line treatment options for ET and PV. This is well established. Here are two sources that speak to this choice.legeforeningen.no/contentas...

mpnjournal.org/how-i-treat-...

Note in the How I Treat ET article by Dr, Harrison that she presents the options to the patient and has the patient decide which to choose. This is as it should be. Both are valid first-line choices. It is the patient's preference that should guide this decision.

The issue is not in convincing any doctor about whether HU or PEG is better, Both are viable choices. The decision is based on the patient's goals, priorities, and risk tolerance. It is the patient's preference that drives the decision making, not the doctor's. This is your right as the patient to determine which choice you prefer. The doctors job is to consult with you and respect your right to make your own treatment choices when you have more than one viable option.

I have a fabulous care team that works with me in precisely this way. I respect my providers and they respect me. I am the one who makes all of the treatment decisions, working collaboratively with my providers. This is both my right and my responsibility.

Hope that helps.

ETguy profile image
ETguy in reply to hunter5582

The 1st report I've not seen. They do collectively support the INF story.

From the 2nd one, more fuel to the fire. Note the suggestion to start early which I take to mean minimize the HU duration.

Some out takes I found notable:

"In the context that data generated from a large number of studies during the last 25 years convincingly have shown IFN to normalize elevated leukocyte and platelet counts in concert with a decrease in spleen size and a reduction in the JAK2V617-allele burden –"

"One single agent – IFN – has been shown to induce complete hematological and deep molecular remissions in a large proportion of ET and PV patients with reversal of disease progression, being sustained off therapy for several years in a subset of PV patients."

"IFN-alpha2 treatment of ET and PV is associated with a decrease in the frequency of thrombosis and bleeding – the major determinants of symptomatic disease burden in MPNs – and a decrease in reticulin fibrosis."

..." treatment with IFN in the early disease stage may be associated with a better treatment response, likely explained by a lower JAK2V617 mutation load and the absence of additional mutations."

For MF patients here, a search of the "papers" would be good but no citations are listed:

"several important papers showing that patients with hypercellular myelofibrosis may actually greatly benefit from IFN-alpha2 being able to normalize elevated blood cell counts in concert with a reduction of spleen size and – importantly – regression of bone marrow fibrosis."

hunter5582 profile image
hunter5582 in reply to ETguy

The other big take-away from the Dr. Harrison article is about patient choice. HU and PEG are both considered viable options by most docs - it is up[ to the patient to decide which is preferable.

Just seconding what Hunter wrote - I recently switched from HU to Peg for many of the reasons you state here. I was able to speak with my MPN specialist using much of the data and my preference to switch to HU and he, like Dr. Harrison, laid out the three basic options, pros and cons to each and worked with me to decide a course of action. So far so good on switch although it is still early. Our MPN and MPN journey is unique and we all react individually to any therapy - the good news is that we have options. Definitely continue to advocate for yourself!

Thanks for sharing this very helpful study, it is rare to have such long-term data. Very reassuring to read for those of us on interferon! But also reassuring for those on other treatments as they also support long-term survival.

Thank you for your post. I think a number of us were already aware of the research you describe, but you explained it all very well . I am planning to switch to pegIFN sometime soon, have only recently started on HU (five months ago) which I tolerate very well so far, but think I should play all my best options now on the basis of the study you quote . Also, I feel that I would rather give IFN a go now, whilst I am still relatively young (ok, I am about to turn 60...) and still with enough energy to deal with any side effects that may arise, rather than wait for new issues to creep in later on. Fingers crossed ! Glad to hear that many of you are having a positive experience with IFN.

My MPN Specialist told me that 65 is the new 35. That makes you 29 going on 30.

If you think you prefer PEG to HU then go for it. PEG is certainly working better for me and is much easier to tolerate.

All the best

Manouche profile image
Manouche in reply to Aldebaran25

« In contrast to previous observations with other pegylated IFNs, ropeginterferon was efficacious and well tolerated even in the elderly cohort. Moreover, the safety analysis in patients ≥60 years showed a positive trend regarding fewer and less serious treatment-related AEs compared to HU. The divergent observations on efficacy and safety between early generation pegylated IFNs and ropeginterferon are potentially the result of optimized protein-engineering, reducing non-specific pegylation and thus improving the pharmacological properties and tolerability of ropeginterferon. »

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

ETguy profile image
ETguy in reply to Manouche

I've seen this study but your pointing out this detail is quite helpful. It might be neat if one of us sees a tidbit that stands out in a study, we can post the detailed quote as we have done above. I usually focus on studies less than 3 years old if possible as things are changing so fast, but there are older good ones too.

Another example, using the search term MAP44 suggested, leads to below. I've read about possible stopping of therapy, (unthinkable with HU) here is an example.

ashpublications.org/blood/a...

VAF= variant allele frequency (I didn't know)

"Overall, our study demonstrates that IFN discontinuation represents a safe strategy in MPN patients who achieved CHR, and particularly in patients with a driver VAF lower than 10% at time of discontinuation. Importantly, relapsed patients did not develop IFN resistance."

With some of this new info for me, I think it's a no brainer to try INF, esp once Ropeg is out. I look fwd to no more HU dizzy head etc.

ETguy profile image
ETguy in reply to Aldebaran25

INF in US has historically been reserved for the under 60's and these patients are likely to get less resistance to an Rx of INF. But as Hunter says, we should get the choice, and my 60+ self would expect to change Drs if he can't give a good reason for denying the choice. Other key detail is insurance, I'd guess you need full Dr cooperation along with sort of the data and comments we're collecting right here to get it approved.

Manouche noted here the good results for oldsters on Ropeg. So oldsters have even more reason to insist once it's approved.

As I've mentioned elsewhere, be sure to get your allele burden before starting INF for reference. I've had it both from BMB and blood draw.

hunter5582 profile image
hunter5582 in reply to ETguy

NOTE: I had no trouble at all getting PEG approved by my insurance - Cigna Medicare Rx, purchased through my former employer as part of the retiree plan. Even though the Medicare Part D plan seems to have a more limited formulary than my previous (pre-Medicare) prescription plan, I was still able to get the PEG approved.

My daughter, who also has a MPN, has a doc who told her that even though she was young (still in 30s) they would be able to get PEG approved even with her low-end insurance plan. She might have to "fail" on HU first, but they would get it approved. Failure = any adverse effects by this doc's definition.

I do hope things will get easier for everyone once Besremi is FDA approved for PV. Meanwhile, it really should be possible for most to get instance approval for PEG. It is a lot more expensive than HU (HU=$86/month, PEG = $4,400/month). That really should not matter. We oldsters deserve more efficacious treatment just as much as the younger crowd.

dmac_77 profile image
dmac_77 in reply to hunter5582

Does your insurance cover most of that or do you really pay 4.4k/mo?

hunter5582 profile image
hunter5582 in reply to dmac_77

$4,400 is the full cost if you have no insurance. I pay $100/month. Until I reach my cap of $2000/year. Then it is covered 100%. I have 2 other meds that cost $100/month so I always reach my cap.

dmac_77 profile image
dmac_77 in reply to hunter5582

Ok makes sense. I couldn’t imagine someone having to spend that monthly. $100 is very reasonable. Thanks!

Thanks for posting this I found it interesting.

My diagnosis is PMF but my specialist is mostly interested in controlling my hematocrit. I was on HU for 4 years, experienced toxicity and switched to Pegasys. My specialist believes that remission is a possibility in my case. I believe I am doing better overall, even aside from avoiding HU toxicity.

The studies you mention are encouraging. I would certainly suggest interferon over HU or phlebotomy to anyone offered a choice. Based on my experience I think doctors are overly reluctant to treat old people like me with interferon.

When I was diagnosed I googled everything I could. The best results showed up when I googled “remission” with MPN or MPD.It talked about INF’s. I feel pretty good right now but when the time comes I will be choosing the only drug that has a miracle chance of clinical remission. 😀

Thanks for sharing this research. I switched from HU and phlebotomy to interferon about 5 months after diagnosis. I was/am high risk, as had/have a CVST (blood clot in the brain). I was diagnosed at 43, now 45. I had to really research and fight to get Peg Interferon and got a second opinion from Claire Harrison at Guys hospital, who agreed to interferon and now oversees my care. I had to be really persistent, my doctor said no three times with my request. I know how difficult it is to fight and navigate the NHS systems when you're very unwell and totally new to the health care/medical world (in a pandemic!). I hope that some who aren't able to persist can find an advocate to support them.

ETguy profile image
ETguy in reply to Dream23

How are you feeling on the INF?

Dream23 profile image
Dream23 in reply to ETguy

Good now. It's been mixed. I felt great at first coming off HU and being able to stop frequent venesections which I didn't take well to. I've never had any flu like symptoms. I was on a high dose 130mg every week and developed serious side effects of serious depression (no history). I was told to stop immediately and take a break, then they have been slowly lowering dose. I felt better soon after stopping and am ok now. Taking every 2 weeks, alternating between 90mg and 45mg. I had hair loss on high dose which has now improved on a lower dose.

ETguy profile image
ETguy in reply to Dream23

There's a pattern in our forum here and literature that INF has historically been given in too high of doses and that is one reason it's been dismissed by US Drs. Your current doses match most of what I've seen here.

Hi, again, apologies for my emotional outburst when I last spoke, but, hey, thanks for this, nice work, great sharing!…..especially, personally as I’m waiting on an IFN script to replace the HU.

This may be the lay mans version.

patientpower.info/myeloprol...

ETguy profile image
ETguy in reply to Magentas

I'm not aware of any outburst, but I won't look too hard for it. Thanks for consideration anyway.

That link is another source to support for our interest in INF.

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