10 facts MPN patients need to know about FDA approval of Ropegylated interferon alpha2b (Besremi).

[Manouche]

Ruben Mesa, MD, FACP, executive director of Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center, and MPN expert and investigator, discusses the top 10 facts that patients with myeloproliferative neoplasms (especially those with polycythemia vera) need to know about the FDA approval of Ropegylated interferon alpha2b (Besremi).

youtu.be/KhKwDj5xZdg(Not working as expected?)

[Snook37]

Crossover dosage from Pegasys to Besremi is very useful!

[EPguy]

Thanks for the great link. I've been following Ropeg closely since my Dx last year.

One note from Dr Mesa is the PV approval for Besremi "was relatively broadly worded". This is a good thing. One part of this is the option to use it "regardless of their treatment history". (FDA)

In all the studies I've seen, the allele burden seems to be a secondary issue that is not emphasized. It was not a factor in the FDA approval to my knowledge. There are no direct studies on its implications I have seen, these will take many years.

In my opinion, and some experts have said, allele is worth considering since we supposedly have a disease driven by allele, and INF is the only agent able to reduce it in the marrow. We've seen here that UK does not routinely monitor it closely.

I have made a graph of the allele data in the Besremi studies, for some reason the allele is shown only as a table. (This graph is my rough doing from the real data, but it is not in any real studies) The JAK2 Allele advantage of Ropeg INF is overwhelming here and acts faster than I would have expected based on the common idea that INF is "slow acting".

My take is even if your blood numbers are good on HU, the advantage seen here makes Besremi quite worth discussing with your Dr. I think this study is also by itself one of the better studies on HU vs allele.

PEG also has allele reduction but I believe those studies are not as long term or as large.

See my post below for survival and progression implications in one study showing good effects from INF.

healthunlocked.com/mpnvoice...

Ropeg -Allele vs time

[Manouche in reply to EPguy]

The allele burden response is very good with Besremi, but is it better than Pegasys ? According to the molecular response some of us got with Pegasys, it tends to be even better than Besremi. Paul123456 managed to improve his AB from 80%to 12% in 30 months. Today, my haem told me that my JAK2 decreased by 86% in 24 months (84 to 11). So I’m not sure Besremi should be preferred over Pegasys for this reason only.

[EPguy in reply to Manouche]

I agree fully. I was impressed with Paul's results, and yours adds to our real life sample on the Voice. It could be that PEG actually works better. Problem for the insurance cos and some Doctors is there are no completed phase 3 studies of PEG vs MPN (If anyone knows of some that would be very helpful) The graph above is good at least for its striking visual message for INF in general.

**If there are more Voicers here with before/after allele data we'd love to know, whether good or not good alelle responses.

Besremi (Actually the Euro group AOP to my u'standing) spent the money to do a phase 3. They had several patients that went to less than 2%. This seems to be a magic number for some researchers, while at least one of the reports from ContiPV (Besremi) suggest 10%. (See quote and link below.) You and Paul could well be on your way to 2% too with PEG.

A key advantage Besremi claims is better tolerance, but if one is tolerating PEG, then what's broken there? PEG is likely also to be cheaper cost.

-----------

library.ehaweb.org/eha/2021...

“A sizable proportion of patients with PV achieved operational cure after 5 years’ ropeginterferon alfa-2b treatment. Lower age and lower allele burden at baseline predicted allele burden <10% at 5 years, suggesting that ropeginterferon alfa-2b should be initiated early in PV to achieve the greatest long-term benefit.”

[Manouche in reply to EPguy]

Shiftzz is already at 2%. It’s theorically possible to fully eradicate the malignant clone.

« In the model, the number of malignant stem cell vanishes at year 12. However, with a lower limit of detection of 0.01% the limit for detecting malignant cells is reached at year 7, while with a lower limit of detection of 0.1% the limit is reached around year 4. Thus, the model predicts the eradication of the cancer at year 12, while the number of malignant stem cells becomes undetectable between year 4 or 7 depending on the accuracy of measurement. »

12 years is a long time. That’s why the lower toxicity of Besremi is so important.

mdpi.com/2072-6694/12/8/211...

[EPguy in reply to Manouche]

I recall the recent report from Shiftzz, amazing.

When we look at the number of patients in the various MPN studies, there are not many. 13-17 for example in the PegIn vs Intron chart here. It makes any info we get from our group significant. What's missing of course is the scientific process, but still any results our members can add can inform us.

That is a really good report. It seems to be a model for predicting results and comparing that to empirical data.

There is one part you noted that seems to conflict with the Conti-PV Allele vs time chart above:

<<...while the number of malignant stem cells becomes undetectable between year 4 or 7 depending on the accuracy of measurement>> In the Conti-PV study the median allele is 7-8% in years 5-6. This is detectable. But likely there are factors or terms I don't understand here. Maybe there is report explaining this discrepancy?

The report also has this chart. I find two items interesting, effect of age and type of INF:

-- <<The reduction in the JAK2V617F allele burden in response to interferon-α-2a (Pegasys) seems more pronounced than that of PegIntron>>

Intron is the red boxes bottom chart, these are inferior to the green pegasys (PEG) ones. Could be difficulty adhering to daily Intron therapy, but maybe a more basic issue.

-- The left/right set in each color is age under/over 60. In contrast to Conti-PV, older patients here did better (on PEG) than younger. In the Ropeg study older correlated to less response.

PegIn vs Intron

[Manouche in reply to EPguy]

« <<...while the number of malignant stem cells becomes undetectable between year 4 or 7 depending on the accuracy of measurement>> In the Conti-PV study the median allele is 7-8% in years 5-6. This is detectable »

I don’t see any discrepancy. On one side you have a mathematical model, and on the other side you have the outcome on a small cohort of patients. It sums up the difference between theory and practice.

[EPguy in reply to Manouche]

Thanks for the info. I'm not so good with statistics. I think it is a sort of extrapolation of the data from a small DALIAH study cohort.

From that I checked the DALIAH study briefly. Its results for INF were not so good. But it seems to be for non pegylated INF (or is the 2b version PEG?) which is no longer in much use.

I'm not clear how the extrapolation in the mathematical study came to such a good conclusion from that data. But the authors' style does seem confident. I do like their conclusion.

[EPguy in reply to EPguy]

I agree also about the lower toxicity, that's a good point as it can go for a very long time. At least one member here could not tolerate PEG but did ok on Ropeg.

A possible good factor may be the other therapies being studied, in the next 10 years there may be faster acting medicines that are available, for example IMG-7289, and in very early stage, ATO+INF.