Great group of videos

[Paul123456]

From the recent St Antonio Patients Conference

mpnadvocacy.com/2018/03/vid...

Re the Jason Gotlib Presentation

Interesting slide re PV showing that WBC increases as Allele Burden increases but Platelets decline as AB rises. Mirrors my recent blood counts.

Discusses risking and higher risk mutations.

Re the John Mascarenhas Presentation

Make sure you watch the last part dealing with RG7388. Only 12 patients in the Phase 1 Trial so have to be extremely cautious about popping the champagne but pretty impressive results, especially when combined with low dose Peg. Phase 2 trials starting across 12 centres so fingers crossed.....

Re Dr Verstovsek Presentation

Discusses MF treatments, last few slides refer to a new drug called PU - H71 which has only been used in the Lab on mice but with pretty spectacular results. This will now enter trials so fingers crossed, looks like closest thing to a possible ‘cure’ (other than SCT) that I’ve seen. However it is very very early stage and most successes on mice don’t translate to humans. But does give a bit of hope...

Re Dr Jeanne Palmer

Discusses STC and in particular, Graft v Host and timing/impact of genetic mutations. I thought quite uplifting.

Re Panel Discussion

Dr Verstovsek (about 10 mins in) discusses Inf and HU. He thinks Inf can only be given for average of 5 years, 5 - 10% drop out rate pa, still get progression regardless of molecular response or normalised bone marrow. (I’d have liked to ask him whether slows progression and how does he compute his 5 year average ie include drop outs from side effects?)

He doesn’t believe HU increases AML risk but does believe that increased long term risk of skin cancer. I think this is the more benign kind, not melanomas.

Incidentally I had my first 45 mg dose of Peg last night, no obvious side effects yet!

[Rachelthepotter]

Thank you, Paul for the flow of information. Will look at it this evening. Lots happening.

[Ebot]

Thanks Paul. Re: the HU vs Interferon debate. I asked Prof Harrison about this. She felt the jury was out on progression and there was little compelling evidence that one was more effective than the other. I also asked another member of her team about HU and skin cancer. Again, as per your analysis my concerns were met with something of a shrug. There is very little risk of melanomas. Essentially cover up / put on sunscreen / a hat - which everyone ought to do in any case - and get on with it.

[Paul123456 in reply to Ebot]

I’ve also discussed this with the Prof. She felt about 25% chance that Peg will reduce Allele Burden but I didn’t clarify re normalising marrow.

Dr Verstovsek implied that molecular response/normalising marrow doesn’t alter progression but I don’t understand how this doesn’t at least slow progression to some degree?

My reading is that Hems split into 3 camps -

1. Inf slows progression,

2. Inf may reduce Allele Burden but only for subset and no clinical data (> 5 years) YET to prove this impacts actual progression

3. Not enough data and if does work (re lowering Allele Burden), only for c. 25% plus side effects and intolerance make HU clear front line choice.

We know from the Ropeg v HU Trial that Ropeg a late starter, after 6 months HU leading, at a year level pegging, 2 years Ropeg clear leader re molecular response.

For me, it’s about balancing my individual risks (age, WHO Stage 1, rising AB to 72% and rising Neuts) against perhaps only 25% chance that Peg will in some way slow progression and the significant risk of long term side effects (thyroid, autoimmune and depression). I started low dose Peg this w/e, was swayed by the group of Hems claiming Peg does alter progression (Drs Silver, Hasselbalch) since they use it early when bloods/symptoms only really justify aspirin/venesections. Hence their data set is different versus others who start with HU (as front line drug) or venesection.

It’s a real conundrum for all of us, patients and Hems! There just isn’t the clinical data. We patients must be careful to avoid grasping straws and our Hems have to dispassionately balance a whole basket of risks (incl re INF high discontinuation rates, ease of application, unknown long term toxicity) versus possible clinically unproven benefits.

PS - had virtually no reaction to my 45mg Peg, no paracetamol required. Strange how we all react differently, wondering why?

[Timjonze in reply to Paul123456]

Agree it’s hard to make a confident decision when different Doctors make different cases. I’m also drawn to the idea of Peg after reading several articles by Dr Silver but haven’t discussed it with anyone at UCLH and presume they will not be in favour just yet. Best of luck with the treatment Paul and look forward to hearing how you get on with it

[Ebot in reply to Paul123456]

Yep. I’ve just started on HU and felt it was a bit of a leap, if not into the dark, then slightly into the twilight. I fully accept that in five or ten years I might look back and think, ‘Ah, if only I knew then what I know now’. And that could cut both ways HU or interferon - or indeed something entirely different. I have to nail my colours somewhere and trust in someone whose expertise I respect so am going with the Prof who I suspect is in camp 2/ 3. In any event none of this is written in stone. And my big questions were first, ‘’Have I an alternative option if treatment A doesn’t work / isn’t tolerated?’ And second, ‘Are any side effects reversible?’ I suspect one could drive oneself into the ground trying to analyse all the variables. And ultimately you have to live on a daily basis with the drug of choice. So glad it seems to be going well for you.

[Paul123456 in reply to Ebot]

Ebot

100% agree. Having confidence in your Hem is vital and the Prof is the best! Only she can see the big picture and then target your individual requirements. The great thing about HU is that it’s been around a long time so we know you won’t become radioactive!

As I’ve said before, I’m hoping the drug landscape will be very different in five years time. You might be thinking about switching to Ropeg when it becomes available say 2019/20 if the year three results continue current encouraging trend. In a perfect world, we will all be on RG7388 if Phase 2 results as good as Phase 1. Should know about Methotrexate and Metformin by then, both ‘cheap’ and could be quick roll out.

Most of us are lucky in that our disease is progressing slowly but medical advances are progressing rapidly. JAK+ve mutation only discovered 2005. Perhaps too much bias has gone into finding JAK inhibitors (beneficial though they are) but now more research is going into drugs, like RG7388, which target other mutations and are potentially more exciting re slowing progression/remission.

[katiewalsh]

Thanks Paul for sending both the materials and a synopsis of each. Best of luck with Peg. Katie

[beetle]

Thanks Paul for posting all these informative links that you pass on to us all. More information = more confidence in discussions with our own haematologists. Keep them coming, please

[PT99]

Hi Paul

Thanks for the info and will look at these later. In the meantime, did Dr Verstovsek explain why Interferon can only be taken for 5 years?

Thanks

Pete

[Paul123456]

Pete

No, his comments are baffling in view of the number of posters on other boards who have been using INF for way over 5 years. Some have had INF ‘holidays’ when drug has stopped working but this appears to apply to HU as well for some people.

I can only assume he is including all drop outs for whatever reason.

I had my first dose of Peg Sat night with minimal reaction. How are you getting on? Interesting that you had a pretty severe reaction first time but amazing impact on your blood counts. And then strange they rose next time! Can you please update us when you have next blood count. I get my next count in about 3 weeks but not expecting much of a reaction

Best

Paul

[PT99]

Thanks Paul. Yeah I’ve not heard that before, I think a lot of people expect to be on it for the long haul.

Glad your first dose went well. I’ve not had a bad reaction since the my first dose but still get shivers every so often and I have to say, I’ve been feeling a bit down, which is a bit worrying. I may speak to the hem about trying to get hold of pegasys if the risk of depression is less likely.

I’m having blood tests tomorrow, which I’ve not had for a month so hopefully have a better idea of how it’s working.

Pete