Polycythemia vera: past, present and future

[Manouche]

 »There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of JAK2-mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials »

tandfonline.com/doi/full/10...

[GardNerd]

Thank you for posting this. It is truly very good news. It’s so good to see the progress being made.

[monarch5000]

13 years out of date information. 13 years ago it was already known that for a majority of patients interferon slows or stops disease progression:

"It is argued that in 2011, the bulk of evidence for the efficacy and safety of pegylated interferons in treating patients with these neoplasms favors the upfront use of pegylated interferons, the goal being to influence the development of the disease at the molecular level and revert patients to a stage of minimal residual disease/operational cure instead of progressive clonal evolution, genomic instability and leukemic or myelofibrotic transformation during long-term treatment with hydroxyurea." pubmed.ncbi.nlm.nih.gov/220...

[EPguy in reply to monarch5000]

What's new is there are now two different ways to get reductions, with the recent Rux study the first to look prospectively for disease modification vs VAF. IFN studies have not been prospectively designed with this precise endpoint, although it's clear enough to us the same benefit is there as supported by the retrospective studies.

The proposed action: ..."suggesting an urgent need to incorporate prospective molecular monitoring into PV trials." is still new to many Drs and patients and does need continued emphasis since many Drs are still not agreeable to the value of VAF measurements.

The report is paywalled, they may have some other worthy insights behind that money.

[hsdale3 in reply to EPguy]

Hi, I kind of sussed Interferon from IFN, however, can you expand on VAF?

Thanks!

[RoundTheWorld in reply to hsdale3]

It stands for Variant Allele Frequency i.e. the percentage amount of genetic mutation you have.

[hsdale3 in reply to RoundTheWorld]

Thanks!

[EPguy in reply to hsdale3]

There are (too) many ways it's named. A couple others are mutant burden, allelic burden (AB), Mutant allele fractions (MAFs) ...

For the basic Jak2 mutation it can also be called "v617F fraction." Some form of this often shows in lab results. "Substitution of a valine(v) for a phenylalanine (F)" at location 617 of Jak2. Early descriptions used "v617Phe"

[Bluetop]

Thanks for posting.