« Patients with PV often have high JAK2 V 617F VAF (>50%) because of the emergence of a dominant clone with concurrent loss of wild-type JAK2, which in turn is associated with increased risk of vascular events and transformation to myelofibrosis. In MPN, unlike other hematologic malignancies, for example, chronic myeloid leukemia and AML, where molecular response to therapy correlates with improved outcome and directs patient management, the clinical importance of molecular response has been unclear despite the efficacy of several therapies at reducing JAK2V617F VAF. This includes recent data with pegylated interferon alpha-2b where despite showing the superiority of molecular response with this agent, correlation with clinical benefit has not yet been feasible, perhaps because of lower event rates in the frontline population, and has been explored in studies, for example, those involving MDM inhibitors. Here, we observed that ruxolitinib was associated with more frequent molecular responses, defined as 50% reduction in VAF, (P < .001) at their final FU. Importantly, JAK2V617F molecular responders at 12 months were more likely to have CR at 12 months (P = .09), and those responding at their last time point demonstrated improved PFS (). Similar to other myeloid malignancies, additional somatic mutations were associated with higher rates of events independent of age and sex, with mutated ASXL1 conferring a specific risk of major events (). Upon evaluating molecular responses at a stem/progenitor cell level, a substantial reduction in the clonal burden of JAK2V617F HSPCs in ruxolitinib-treated patients achieving a molecular response was demonstrated, consistent with ruxolitinib-induced clearance of JAK2V617F stem cells. »
CONCLUSION
The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to event-free survival (EFS), progression free survival (PFS), and OS.
I had my visit two days ago with one of the authors of the study that Manouche just posted. We discussed the issue of having a high JAK2+ allele burden (79% in my case) and being on Pegasys (in my case). She is quite an expert on the gene panel element (did her PhD on this) and told me that it is quite common for PVers to have a high VAF, and usually a lower one in ET. She was very positive about the capacity of ruxolitnib to impact on VAF, and I thought about you EPguy, you may be on to a good thing with your change in treatment. She seemed (in my perception) more confident about ruxo that Peg. In my case, I will wait. I was told it may take several months (maybe a year) before any real Peg impact on VAF.
High VAF for PV vs ET is a typical pattern. I think PV averages something like 40-60%, but many are where you are and up. IFN is a good bet to reduce that. Hunter went from ~80 to 9.
I have PV Dx but only 14% at that time, I do have some ET features. IFN got it down to 10% in 6 months, ended at 8%.
My Dr from the start has preferred Rux over IFN. But that has generally been true of US vs Euro practice, Euro has many years experience with IFN.
Dr Harrison is supposed to have a report publishing soon on high dropouts for IFN as discussed in other posts. This would be new info for many of us.
When it blew up on me my Dr said "interferon is tough medicine". Besremi was supposed to fix that harshness, we'll learn more right here on the Voice.
You're right on the timing of my forced switch, the positive reports on molecular response for PV are just arriving. I've just posted on the one at top here.
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