Ramblings on Pre-PMF and early stage MF

[Paul123456]

There have been multiple threads recently on Pre-PMF and early stage MF. My very limited understanding is that Pre-MF can be hard to distinguish, even via BMB, from ET.

My original BMB was plain ET, a second BMB 15 months later produced one dx of ET and another of PV/MPN-U (I had two cores taken, sent to different labs). MPN-U (the U stands for Unclassified) appears to be a euphemism for Pre-PMF (see the link below re should Pre-MF be a separate classification, that c. 15-25% of MPN’s are Pre-PMF).

bloodjournal.org/content/12...

Pre-PMF sounds scary but this article states prognosis similar to PV. Imo the important part is not exactly where we are on the sliding scale from ET to MF but how fast we are travelling.

So what should we be focussing on?

First aspect to consider is what is the best drug option. I’ve gone for Pegasys (Interferon). Bit of a leap of faith since expert opinion split re benefits versus risks but it does appear to reduce Allele Burden and improve fibrosis in a subset of patients. It’s effectively three rolls of the dice, 1) can I tolerate the side effects, 2) will I be one of the lucky ones who gets molecular response and 3) how meaningful is this molecular response long term. I’ve had no side effects on 60 mcg weekly (some are taking 180mcg) and I’ve had good early haematological response. Will get Allele Burden checked in two months.

Can I suggest that anyone thinking about Pegasys watches this recent video panel discussion between two Interferon bulls. And then google searches Interferon v HU etc.

youtu.be/7EjnHGP0glk(Not working as expected?)

Re starting Ruxo, my understanding is that one of the problems is that, for some, it only works for c. 4 years? Hence I wouldn’t want to start until I really need it. Also it extends life by improving symptoms, as far as I’m aware it doesn’t slow progression in the way that the bulls claim that Interferon does.

It appears there are effectively 5 stages of progression? Pre-PMF, early stage PMF or secondary MF, Intermediate 1, Intermediate 2 and then final stage. Normally Hems will advise SCT at Intermediate 2 stage but if the patient has developed high risk mutations such as ASXL1, they will likely advice transplant at Intermediate 1. Hence, if we are open to SCT option, we want to know if/when we reach Intermediate 1 so that can request Myeloid Panel test to identify any adverse mutations.

The questions I’m going to ask next time are: Will changing blood counts/symptoms give advance warning signs of progression to Intermediate 1? Or is it possible to progress with stable blood counts and no new symptoms? And if we are controlling our counts with HU/Peg, does this ‘muddy the waters’?

Best Paul

[hall2]

Thanks for this Paul. I have to go for results of a BMB tomorrow and I'm hoping I'll be told that I haven't progressed to mMF, preMF or whatever!

Angela

[Cecilie]

Thanks for posting this, Paul. As someone with an MPN-U diagnosis I'm finding this very interesting. I have to admit that I've been feeling very confused since my diagnosis changed from ET to MPN-U after my BMB. Why is it so difficult to interpret the BMB results? Is it not the case that some MPN specialists believe that some fibrosis can be present in the ET patient group? I wish it had been explained to me properly at the hospital. On the positive side I'm lucky enough to be taking interferon, which seems like the best choice.

One more question: how do you check your allele burden?

Kind regards, Cecilie

[Paul123456 in reply to Cecilie]

Cecile

I agree it’s confusing. I assume that it’s like spectrum of light. Lots of different shades with very subtle differences. My best guess is that Pre-PMF is covered by MPN-U but that MPN-U may not be Pre-PMF. I’m WHO Stage 1 fibrosis and twice dx ET by one Lab.

The AB test is a separate blood test. I assume you have been tested for JAK2+ so your hem will have the %.

Angela

Good luck tomorrow, fingers crossed.

Best Paul

[Rachelthepotter]

Thanks so much for this, Paul. Very clear and very helpful. I look forward to the next instalment

Rachel

[crapaud]

Interesting comments about Pegasys 'muddying the waters?' - I don't know to be honest. In my personal case I was taken off Pegasys to prepare for my SCT and my WBC went berserk - I went from being off the normal low end range to twice the high end range in 2wks!!

Don't know if being taken off Pegasys had anything to do with it, or it was just a coincidence - things were pretty rough at that time. The most dramatic weight loss I've ever experienced in my life, - 20kg (3St) in 3wks. I wouldn't recommend as a diet!!!

Put some of the weight back on now.

Gary

[SusanFletch]

Interesting and I do find your posts very informative. One question I ask myself though is how far should someone newly diagnosed with myelofibrosis put absolute faith in how long Rux will work for them based on current statistics?

We are a small population and the presented data has to be historical.

I wonder what we should be asking our consultants when diagnosed with myelofibrosis about the expected long term performance of Rux for us when deciding whether to start taking it or hold off until symptoms become developed.

Susan

[Paul123456 in reply to SusanFletch]

Susan

The good news is that there other other JAK inhibitors in the pipeline so that by the time Ruxo stops working there should be new drugs that might/will be better.

cancertherapyadvisor.com/he...

Best Paul

[Bigmann1 in reply to SusanFletch]

Hi Susan

Have you started treatment yet? If so, how are you doing?

[Wyebird]

As always a mind of knowledge. I enjoyed listening to the video. Thank you Paul.

[Elab]

Thank you for that Paul.

It’s so good to read so informative posts.

I didn’t know there are 5 stages of Myelofibrosis. Video was also brilliant.

Thank you again