I saw some members discussing the dosage of interferon previously, and those discussions have been very helpful. I want to share that when accompanying a family member to a medical appointment last week, the doctor talked about some recently developments.
The doctor told me that the manufacturer of Besremi, the P-E company's research team, had talked to another group of European KOLs about the suitable treatment dose of IFN.
The conclusion is that the P-E research team agrees with the European KOLs' perspective, which is that due to the significant differences among PV patients and safety considerations,it is not advisable to uniformly use high starting doses or rapid escalation of dose in the PV treatment.
Instead, the treatment of PV patients needs to be individualized and it follows that it is more appropriate and safer to gradually increase the dosage to see if the desired effect can be achieved. The only point of disagreement raised by the P-E team is that high doses might still be an effective and alternative for some patients.
I found the literature the doctor was referring to and share them below. One of them require subscription to read though (I am luck that the doctor allow me to have a copy of it).
The dosage of ropeginterferon in polycythaemia vera: Balancing efficacy, safety and pharmacoeconomics across risk categories (European KOLs' opinion on the dosage)
The higher initial dose and accelerated titration regimen of ropeginterferon as a treatment option for certain patients with polycythaemia vera (A response to European KOLs by P-E's research team)
The first reference gets interesting right at the point the free version cuts off. "To identify patients at diagnosis most likely to respond to lower Ropeg doses, stratification based on the..."
Both refs refer to the main Ropeg study, Proud PV as not being accelerated, but its dosing, image here, was nearly as aggressive as the high dose study (HIDAT regimen ). Main diff is just the first two months.
Rather than compare two high dose trials to each other, better to compare either to a low dose study. The 1st ref notes "The Low- PV trial compared a fixed dose of 100 μg every 2 weeks to phlebotomy- only" Low PV had only 28% reach CHR at one year( with 81% controlling just HCT), while proud PV had 62% in CHR.
There are plenty of variables to mix these up but it seems low dosing was inferior for CHR (28 vs 62%).
Notably Low PV measured VAF reductions for only HCT responders while proud PV did not select for VAF response. So Low PV could have a bias to show better VAF results.
Separately Table 1 shows a signif loss of CHR over time. This theme shows up often for all treatments as I've posted.
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Buried in the Low PV report is one criteria they found for non response
"This subgroup (non HCT responders) exhibited distinct baseline features, including a higher proportion of males, elevated body mass index, greater phlebotomy demand, higher blood counts and elevated JAK2 V617F VAF"
The criteria re males and BMI seems new info. Low responders to Plb predicted low response to IFN in Lo PV.
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There's enough data here to keep my foggy mind busy for days, but this is just some thoughts. HCT response was a predictor of VAF reductions in Low PV, a familiar concept. It could be low dosing is inferior to high dosing of either sort as suggested by my observation here, ;but my take is dosing just for CHR, or at least HCT, response remains the best way to control disease while minimizing the risk of extreme safety outcomes. Comments welcome.
I agree with your observations but one question. Have any of these studies looked long enough to see if there is a difference in how long the treatment works for? I was wondering if a low does approach would last longer as a high does approach may be more likely to result in the body rejecting the meds in time.
I agree lower dosing should reduce the rate of being forced off IFN, or even disasters like mine. But there will be exceptions one member recently posted on a bad outcome with very low dose, and my dose was not that large either. I don't think there are any long term "low dose" studies. For those who can stay on there are some observations:
For "not-low" dosing one pattern over time for all treatments has been a peak then some loss of CHR on avg as noted above, and seen in this plot. The other pattern has been similar for VAF reductions for IFN at least, only the better responders maintain reductions after ~5 years while the mean and thus most pts start to rise.
It is possible low dosing could prevent these loss of responses? The one year CHR result was not a good start for the low dose, as above 28% vs 62 for "regular" dosing.
I recently posted on comparing the accelerated dosing to the proud PV dosing and those aggressive first two months seem to have an effect as in this plot I posted. The expected CHR peak is earlier in the high dosing. So maybe on the other side, low dosing could start slower but extend the peak benefit for longer.
There is a lot of slicing and dicing Bes goig on, so more clear info will show in coming years.
But my guess is the best answer will end up as the min dose required for HCT or CHR.
Thank you Sam. This sounds more reasonable. I remember hearing doctors saying that each of us is different and therefore it does not make much sense to require everyone to start with a high dose. Maybe in the future some portion of patients will be more suitable to that high dose treatment, but that is not for everyone. These articles also help better communications with doctors!
for what it’s worth at the most recent doc to doc conference in NY in Oct, Dr Gisslinger was of the view to start low go slow to avoid blowing it with side effects, the other docs seemed to agree with that
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Ropeg versus HU/BAT results after 3 years
