Reduction of allele burden on Pegasys?

[Marossi]

I had an appointment with my haematologist yesterday and was a little disappointed to learn that my allele burden was unchanged (in fact even a little higher) after a year on Pegasys. It is currently at 75% (up from 71%). How are the rest of you faring on Pegasys in this respect? I would be grateful for any feedback.

[Paul123456]

I was dx in 2016 at 56%. Increased to 75% March 2018 when I started Pegasys at 45 mcg weekly. Decreased to 66% by Sept when I increased to 90 mcg weekly. Waiting on result of December test.

My Hem said AB test inaccurate and the 66% AB not significant re molecular response unless backed up by a couple more tests. Hence your result may be within error boundaries.

Do you smoke? This is meant to inhibit Pegasys pathways by increasing inflammation.

What sort of diet do you follow? Do you have any idea re your inflammation levels such as CRP test? I have a, probably batty, theory that low inflammation improves Peg efficacy. Have discussed this with Hems and inconclusive, no one sure whether diet impacts the pathways Peg uses since multiple pathways. However they do know that smoking adversely impacts these pathways so I can’t see any harm in, possibly, getting ahead of the game with anti inflammatory diet. Basically Mediterranean diet which has proven general health benefits incl whole grains (see today’s newspapers!)

What dosage are you on?

Best Paul

[Marossi in reply to Paul123456]

Thanks for your detailed answer Paul. My doctor did say, as you pointed out, that the AB test is not that accurate and that my AB was likely to have remained the same rather than increased.

I started off with 90mcg every two weeks gradually increasing to 135mcg every week. When my blood counts were brought under control in November my doctor told me to space out the injections to every two weeks and recently to every three weeks. This seems to be working as haematocrit is 41 and platelets 315.

I have never smoked and my CRP is low. I generally eat a healthy Mediterranean style diet and am not overweight.

My doctor did reassure me that it will eventually come down, that Pegasys is a slow-acting drug and that I need to be patient. I hope he’s right as I believe some studies have shown a correlation between a high allele burden and an increased risk both of thrombosis and progression to myelofibrosis or transformation to leukemia.

I have to say I was a little shocked to find out that my AB was so high as I had thought that people with PV have a median AB of 40%.

This is all preying on my mind now and I kind of wish I didn’t know the results of the AB test.

Though I guess I should be grateful my blood counts are under control and I am basically symptom-free.

[Paul123456 in reply to Marossi]

Have you had a mutation panel test for TET2? I’ve got TET2 and understand that it can increase AB levels. About 15% of PV’ers have TET2 but it is evidently not prognostically significant.

There are posters on other forums who have had high AB for many years and no progression. Their general opinion is that it lowers our resistance to progression but only in those most vulnerable to progression. You appear to be low risk, especially now that on Pegasys.

Have you had BMB?

Best Paul

[Meatloaf9 in reply to Paul123456]

Hi Guys, when I saw my MPN specialist at the Cleveland Clinic last year he told me that is was not known if lowering the AB had any benefit on the clinical course of the disease or on progression. That was in May of 18, maybe something new has been found out since that time, maybe you know of some published scientific articles that are more definitive on the benefit of lowering the AB. Thanks for keeping us all up on new developments and best of luck to you and everyone else.

[Paul123456 in reply to Meatloaf9]

I think low AB is better than high AB in terms of progression risk but perversely, once in MF, a higher AB is prognostically a bit better.

My very limited understanding is that high AB reduces the ability of p53 to combat cancer/more mutations? RG7388 is so exciting because it boosts p53

[Meatloaf9 in reply to Paul123456]

Thanks

[Susana7]

Hi, I have been on Peg for over 3 years but don’t know my allele burden since it is not routinely measured in the UK. But from my readings, treatment time and dosage will affect the AB levels. One year is not long for slow acting interferons, so you probably just need to give it more time for the AB to reduce. Susana x

[Paul123456 in reply to Susana7]

The Ropeg v HU trial interesting, took over a year for Ropeg to pull ahead of HU re AB reduction.

However some people respond much quicker than others and others can’t tolerate. Why we all respond differently is a point of interest. I’d hope to be getting a ‘significant’ reduction after 6 - 12 months since my high AB level so high if I’m responding well and on target for ‘remission’ in two or three years.

I think Dr Silver recommends building up to 90 mcg for one year and then 45 mcg, subject to haematological response.

[Marossi in reply to Susana7]

Thanks for your encouraging words Susana. You are probably right and I will just need to be patient. No use worrying about things we have no control over!

[Marossi]

As you point out, we’re all different in the way we respond to treatment. 90mcg wasn’t working for me, even with supplemental venesections. I think my haematologist has decided to space out the injections to every three weeks rather than decrease the dosage to avoid wasting the medecine, (the syringes are 135mcg). Ropeginterferon should be available within the year apparently and he told me I could then inject every month/5 weeks as it is even more slow-release than Pegasys.

[Marossi]

Hi Paul, no I’ve never had a bone marrow biopsy. Diagnosis for me was fairly straightforward as I am Jak2 positive and presented with haematocrit of 54, elevated platelets and an enlargened spleen.

That’s interesting what you say about the TET2 mutation. As far as I know I have never been tested for it but will bring it up with my doctor if my AB remains high when next tested.

It’s reassuring to know that others with high AB have not progressed over the years. I do realize that most people don’t. I’m usually a fairly sanguine person and try not to worry about things I can’t change. If anything this news will encourage me to make more of an effort in the things I can change to improve my health namely eating healthily and exercising.

Thanks for the feedback.