Summary Paper from Drs, Claire N. Harrison and Donal P. McLornan

[EPguy]

Nice summary I just came across from some of the experts. I've included some outtakes I found notable. Lots more in there on R&D for MF.

onlinelibrary.wiley.com/doi...

From chart, HCT control matters. This was discovered ~2011 and is likely a big part of what we've discussed as better modern MPN management. Before this HCT was to be under 50, after this, under 45 (we now know females usually target under 42) <<CYTOPV study confirms target HCT>> From CYTOPV <<Those who had an HCT of 45% to 50% had a risk of death from cardiovascular causes or major thrombosis that was four times that of patients who maintained an HCT of less than 45%>>

--

MAGIC ET study:

<<‘triple-negative’ ET, have the best out-comes amongst this disease

group, potentially suggesting they may be at more risk of iatrogenic

harm and a future prospect for such patients may well be the

de-escalation of therapy>>

<<For ET, demonstrated that response to ruxolitinib was no better than standard therapies>>

<<specific patients with (HC) resistant/intolerant ET have a worse overall trajectory>> (certain mutations are listed, I think this relates to the next gen sequencing)

<<JAK2V617F-mutated ET patients demonstrated better platelet control with ruxolitinib>>

<<Both IFN and ruxolitinib may have the potential to impact on the overall disease trajectory for MPN, in particular for ET and PV.>>

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HCT matters: <<with the exception of control of the haematocrit to<045, this facet (blood counts) of disease response has not been shown to directly correlate with thrombosis or progression>> See CYTOPV above.

Reducing allele may matter, for Rux: << ≥50% decrease inJAK2V617F allele burden by 1 year correlated with no thrombotic events and improved progression-free survival>> INF is esp good at this.

<<prior studies (before Ropeg's PROUD PV) of IFN therapy in MF have documented better responses for patients with smaller spleens, indicating perhaps the agent (Besremi) may have more utility earlier in the disease state>> Early INF start matches what the various INF experts are saying.

<<studies did demonstrate that ruxolitinib therapy for intermediate-2 or high-risk MF, as defined per International Prognostic Scoring System (IPSS)risk score, could lead to improved overall survival, indicating for the first time in MPN that a modality other than allogeneic stem cell transplantation could achieve this>>

<<for MF, spleen volume reduction(SVR) and reduction in total symptom score (TSS) are important surrogate markers of longer-term benefit >>

For SCT <<there is preliminary data emerging that JAKi exposure before or during conditioning may in fact reduce the rates of graft-versus-host disease,>>

<<This scoring system (large genetic study) permitted tailored personalised predictions that were more informative than standard scoring systems, or indeed standard disease subtypes ET/PV/MF>>

<<Another drawback of JAK inhibition is that the average response duration to ruxolitinib appears to~168 weeks>>

[Mostew]

Thanks for nice clear summery .

[Manouche]

<<Another drawback of JAK inhibition is that the average response duration to ruxolitinib appears to~168 weeks>>

This is true for MF only and not for PV. The average response duration of Jakavi for PV is said to last at least 5 to 10 years .

[EPguy in reply to Manouche]

Thanks much for the better context. I had a feeling it was not the full picture. My Dr prefers Rux over INF, but says both are good. My main hesitation on Rux is the vax trade off.

Are you aware of any multi year Allele data for PV on Rux? I've seen some but not as coherent as the ContiPV for Ropeg.

For CHR, The ContiPV study for Ropeg seems to show somewhat better at 5 years than the RESPONSE Rux PV study. Very roughly 65% vs 55%. I don't know if they are comparable however.

I just came across Rux cream. Not likely relevant to MPN but interesting.

opzelura.com/

[Buggerbear in reply to Manouche]

Thank you Manouche for clarifying that....I was already counting the weeks and getting nervous!!

[Wyebird]

Thank you

[MPNBlog]

Hi ET Guy. A nice precis of the article. Many thanks for this. Best wishes

[Meatloaf9]

Thank you for posting this. We need all the info we can get.