MPN Hub summary Impact of mutated JAK2 allele burden on the outcomes in PV and ET of a recent article by Guglielmelli et al.
durable molecular response (DMR)
complete clinical and hematological response (CCHR)
"Increased DMR was correlated with longer duration of CCHR, reduced progression to myelofibrosis, and increased rates of myelofibrosis-free, event-free, and progression-free survival.
Factors predicting DMR and reduced progression to myelofibrosis included a baseline JAK2 VAF <50% and a VAF reduction ≥35% after 2 years of treatment.
The findings underscore the significance of targeted molecular response in managing myeloproliferative neoplasms, advocating for personalized treatment strategies based on JAK2 VAF dynamics." mpn-hub.com/medical-informa...
Directly from the Clinical impact of mutated JAK2 allele burden reduction in polycythemia vera and essential thrombocythemia article abstract.
molecular response (MR)
"Overall, these findings support the clinical value of achieving profound, durable MR and its consideration as surrogate endpoint in future clinical trials." onlinelibrary.wiley.com/doi...
Very interesting and relevant finding.
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hunter5582
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They offered this plot. The current report is 2 years newer so the full report likely has more and new details, but it's pay-walled.
One difference is the older report has a starting VAF (mutation burden) of less than 60% led to much greater likelihood of MR, while the newer one uses 50% as a cutoff. But either suggests IFN may be better for reducing from the higher levels, although they don't make this connection.
These reports made the progression-molecular response connection explicit for Rux. It has not been prospectively studied for IFN that I know of although the evidence of prog vs MR for IFN is strong. Implication is how VAF is reduced matters less than reducing it.
It is a large % NMR. The cut off VAF they report for better MR is 50-60%. The VAF at start of Rux was median 68%, well over the cut-off. So a majority without MR is consistent.
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A different report on a larger population has for Rux pts: ">50% reduction observed in 56%" They don't break out <50% but it would add up to something well over 56%. The plot here shows a response that looks qualitatively similar to that for IFN, lots of downward red, and clearly much better than NMR=56% (I assume the two unrelated 56%'s are coincidental)
Interesting hint of what's behind the paywall of the OP report. Google result has: "Overall, these data suggest that very long exposures to RUX are required for the JAK2V617F mutant clone to decrease to very low levels..." This is different from IFN where, if the reduction has not occurred after ~2 years it is increasingly less likely to happen.
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The earlier version of study has this intro "Ruxolitinib (RUX) is approved for patients (pts) with Polycythemia Vera (PV) who are refractory or intolerant to hydroxycarbamide". As in this post, refractory to HU has a very high hazard ratio of ~6-7 for bad outcomes. So this population is biased to unfavorable outcomes.
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Ropeg versus HU/BAT results after 3 years
