MATEs FORUM

Evening all...

Remembering as always, that we really MUST be our own very best advocates, if we are to receive the very best "Standard of Care"
As mentioned & promised in our last Cafe Catchup meeting... Here is the information concerning Next Generation Sequencing (NGS).
We MUST learn to push our medical teams to improve their level of understanding of all things MPN, and how best to treat MPNs follows automatically, in my view...

The aim of this review by the MPN Working Party of the Australasian Leukaemia and Lymphoma Group is to propose situations in which NGS
panel testing should be considered standard of care in MPN management, and to highlight other situations in which there may be clinical benefit from testing now or in the foreseeable future.

(Ross et al 2022)

The following Links, will provide a greater "in-depth" appreciation of what NGS is, and why it has become so important in dealing w/ MPNs.

This professor, and a number of his colleagues believe that that the prohibitive costs of performing an NGS, might be prerventing some MPN patients from being able to seek the assistance they need to manage their various MPNs illnesses:

It’s emerging in all cancers, but particularly in the MPNs, that “genomics is everything” according to Professor Andrew Perkins, an expert in myeloproliferative neoplasms (MPN). And for that reason, he says next generation sequencing (NGS) needs to be funded through the Medicare Benefits Schedule (MBS) for all myelofibrosis (MF) patients in Australia.

One of the co-authors of a recent Paper was kind enough to provide me w/ access to gain a more comprehensive picture concerning the import of MPN patients being able to receive the "Best Standard of Care" by having their NGS costs covered by the Medical Benefits Scheme (MBS), here in Australia.

Currently, an NGS panel profile for "High Risk Molecular" mutations, can range between $AU500-800.00, as I understand it...

“The common JAK2 gene mutation drives about 50% of myelofibrosis cases, but there’s a whole swag of 30 or 40 other genes that are important to know about,” said Prof. Perkins, Director of Genomic Medicine at the Alfred Hospital (Melbourne).

“We need to know about a combination of mutations that are very good at predicting your five- or 10-year survival, since these are critical to inform treatment decisions.

“If you have a mutation in these genes, your myelofibrosis can progress quickly to either acute leukaemia or just get worse, despite treatment with approved JAK inhibitors such as ruxolitinib (Jakavi®).

POST-ET AND POST-PV MYELOFIBROSIS
(PET-MF AND PPV-MF)
The diagnosis of transformation from chronic phase ET or PV to secondary MF rests on clinical and haematological findings, so the principal role of NGS panel testing is to inform prognosis. The clinical features of secondary MF closely resemble those of PMF, but the data regarding mutations in secondary MF are less extensive than for PMF. Biologically, it seems likely that those mutations that confer an adverse prognosis in PMF would have a similar effect inn secondary MF, but this remains to be verified.

Prognostic models for PMF, such as MIPSS70+, do not include patients with secondary MF. The Myelofibrosis Secondary to PV and ET-Prognostic Model (MYSEC-PM) was developed to improve accuracy of prognosis for secondary MF.38 It incorporates driver mutation status (CALR unmutated status regarded as adverse) as well as clinical features, and can divide patients into four risk categories with median survival ranging from 2 years in high risk patients to
>14 years in low risk patients.38 This score does not incorporate other potentially high risk non-driver mutations.

(Ross et al, 2022, pp. 343)

CONCLUSIONS
The reporting of myeloid NGS panels requires knowledge of both genetic analysis and MPN pathology and therefore is best delivered in a specialist referral centre. Maximising the value of testing requires integration of these two sets of knowledge. Considering the additional assay cost of NGS testing at present, it is desirable to establish criteria for situationsin which the clinical impact of NGS panel testing is greatest and is justified from a health economic perspective.
Myeloid somatic NGS panel testing should be made available when needed to establish the diagnosis in conditions such as triple negative ET/MF; JAK2-negative PV; and CNL. NGS panel testing is currently routinely recommended for risk assessment in transplant-eligible patients with MF. NGS panel testing should also be available when needed to identify specific targets of therapy, which is currently limited in MPN. Other applications of NGS panel testing in
MPN may have additional value but have not yet been incorporated into routine clinical practice due to lack of funded access to testing. In the future, as the cost of NGStesting reduces, it will become practical to use somatic panel testing more widely as the first-line diagnostic test for MPN patients.

(Ross et al, 2022, pp. 346)


REFERENCE

Ross, D et al. 2022. "Myeloid somatic mutation panel testing in myeloproliferative neoplasms". Pathology (2021), 53(3), April

Leukaemia Foundation. 2021. "Expert interview: Professor Andrew Perkins on MPN", October 29, 2021
https://www.leukaemia.org.au/stories/ex ... _blSlGrVTE#

Hi Steve

Thank you as always for taking the time to keep us updated with any new formation.

Can I just ask, are the NGS the tests used to diagnose JAK 2 & Carl mutations or are they to test for further mutations within the JAK 2 and Carl mutations? I'm just trying to get my head around it all before I speak with Cecily.

I absolutely agree that we need to be our own best advocates. Though I have been feeling drained by it all. My GP forgot to sign my referral for Cecily to get a second opinion, then she forgot to send it so I need to follow that up. Then I caught Covid so that has put me back a few weeks. I'm mentally over it all. I need to rally and get back in the fight!

Hey MiaGrace...

Yes, we can all empathise, on the being overwhelmed by it all... Completely understand!

And now you've had CV–19 too... Poor girl, how did you manage to achieve that feat? Far more importantly, how are you feeling? Was it a bad bout etc?
Do let us all know please... Are you well recovered now?

Next Generation Sequencing (NGS), is specifically used to test for a range of other mutations, (last count, I seem to recall there being circa 28 of them). Among those Mutations tested for are some that are considered as, "High Risk Molecular" mutations, & some of those can have an adverse bearing. However, it is also my understanding, that many of those mutations, also can occur quite naturally as a mere consequence of ageing etc... Therefore, some of them are also quite harmless, even when they are present. What they are really looking for is those that might impact in a negative sense, Because taking affirmative action, in some cases might prove a better option than the standard, "Wait & Watch"...

The JAK2, CALR & MPL Tests, all used to be separate Tests, although, I am not completely certain that they cannot be requested within the NGS screen itself. My understanding is that they can be requested, rather than having to arrange for a seperate assays... Worth asking someone who knows about that(?) Perhaps Kate Burbury at Peter MAC. Cecily may know also...
Because, the former practice was to undertake them separately... More money earned that way too I suppose... Yes, I have little faith in what really makes the world spin etc...

Nevertheless, the NGS Tests, will also provide the 'Allele' burden information, & should be requested to be included in any final report etc.

NGS are presently quite expensive c. $500-800.00. However, the article I Posted about suggests that they may soon become the "New Standard of Care", & then provided FREE of charge. The outcome of an NGS can have impacts upon one's prognosis & also treatment regimes etc. However, exactly when that might transpire, (the FREE thing), could be anyone's guess at present...

I could email the good doctor again & seek his response as to a 'Timeline' if you like...? He may not be any the wiser though too...???

Pity you missed our last Cafe Catchup because there were quite a few people there from all over the globe, & they are all very amiable & approachable etc...

Anyways, if you ever need to chat, you know you can always call either myself or Katie...

Please do let me know how you're doing after your CV–19 bout, ok?

Best wishes...

Steve

Hi Steve

Thank you for clarifying the NGS testing for me
What a difference it could make in our treatment. It would be amazing if/when it becomes free. Having an MPN and all the symptoms that comes along with it can really affect the finances.

I found Covid tough going. I think I caught it while shopping. I tested negative up until day 5 of my symptoms (which was also a Saturday) so I was unable to get Paxlovid from my haematologist. I had fever, cough, muscle pain, nausea, headache and really painful sinuses and lost my sense of taste. Non of my household caught it thankfully as I isolated as soon as I started feeling ill. My last booster was January so I think it had worn off. I'm on the mend now but still have sinus pain and a dry cough.

Hey MG...

Hmmm... methinks that one was NOT wearing one's mask as one was shopping... was one?

Ever since this whole thing commenced, I have not stopped wearing a mask whenever I am in a public situation etc... Seems just an easier way to manage it all... I have no desire to have CV–19, & for me, having a Booster that might provide me w/ a seropositive result, (one where 'Anti-bodies to the vaccine are created), means that I must first Modify my 'Med's'.

Hence, prior to my taking my 3rd Booster of Pfizer; first I had to cease taking an oral chemotherapy drug (MTX), and then also lower my Ruxolitinib from 25mg b/d to 15mg b/d. Two (2) weeks later I had my 3rd Booster, and a further Two (2) weeks later I was Tested for "Anti-body'" Titre, & fortunately I had a positive result,. & managed some protection from CV-19 etc... YAY!!!

However, all of that is a bit of a process, and reducing the Rux' also means undergoing some uncomfortable withdrawals from having done so etc... Nevertheless, I figure that all of that is still better than my becoming ill...

After a few weeks my Platelets shot back up into the 900s range, & so had to re-increase my Rux' dose back up to 25mg b/d again. Thankfully, my Platelets have returned to the 700s for the moment...

Unfortunately, all of this will still continue to disturb our way of life for sometime yet... Because, new variants will keep emerging until the virus is completely defeated, whenever that might be? Hence, in the intervening moments, I shall just keep wearing my mask... Just seems a no-brainer to me...

Anyways, your symptoms didn't sound like much fun either... Sorry that you've had to go through all of that too... Hopefully, you'll be as good as gold again in no time MG...

I shall keep you Posted if I hear any more about 'When" NGS might become the "New Standard of Care"...

Very best wishes, stay happy, safe & well...

Steve

I am very sorry but as long as hydrea is still seen as a 1st-line remedy in the treatment, I see little benefit from a better diagnosis. You can have a favorable gene profile and then develop cancer with Hydrea. I therefore think it is better to focus on better drugs with disease-modifying properties such as Bomedemstat...