Pegasys works on allele burden!!

[JT_Marlin]

Great news!

Been on Peg for nearly two years now - first at 45mcg then up to 90mcg.

My allele burden two years ago was 6, switched to a new lab and got a 10.2 last year, and now at 7.5. We are pleased with this reduction!

[hunter5582]

Glad to hear the MAB is headed in the right direction. I was at 26% the last time we checked. After a couple of years on IFNs, we will recheck and see where things are at. hoping mine will move the right way too.

[EPguy]

If your two labs were giving similar accuracy, (not assured) it means you not only went down, but stopped an upward trend. It's possible you could have been at 14 without the PEG. That 7.5 is a good trend indeed.

[Meatloaf9]

Glad to see that you are having a positive effect on your allele burden, is the Pegasys keeping all of your other blood counts in normal limits, RBC's, Hct, Platelets, WBC's, Hgb etc??

[JT_Marlin in reply to Meatloaf9]

Thanks meatloaf - yes my blood numbers have all come down to either be in range or actually below range and holding steady - exception is my white count which has been low but not getting concerningly low. Havent needed a phlebotemy since last June - my hct is steady well under 45 every time we check.

[Meatloaf9 in reply to JT_Marlin]

Thanks for that info, how often do you have your blood checked? How often do you see your hematologist? Just wondering because I have a new hematologist whose protocol is very different from the last one.

[JT_Marlin in reply to Meatloaf9]

I gather that they decide course of treatment based upon the perceived risk of the patient. In my case, despite having an otherwise low allele burden, I had a heart attack when I was 36 and a stroke at 40 - both presumably the result of clotting. Since the discovery of my JAK2 mutation following the stroke, I have had my blood checked monthly (complete blood count and liver enzymes) - though I dont see my hematologist monthly (that has remained quarterly) - this monthly check is for general blood check, but more importantly for HCT<45 and liver enzymes. Given that my blood numbers have been steady for some time now, I more recently have moved to every 6 weeks for blood check, and presuming nothing changes, the plan later this year is to move me to quarterly blood checks aligning with my quarterly doc visit.

[Meatloaf9 in reply to JT_Marlin]

I agree with you that treatment should be individualized for each patient. My MPN specialist wants me to have CBC's every month presently but my new local hematologist only will order them at 3 month intervals. May have to find a new local doc.

[Flynn2107]

I just got my first Jak2 genetic result after 6 months on Pegasys. My March 2021 bone marrow biopsy showed 88% burden and now my Feb 2022 peripheral blood results shows 76% burden. I was on 500 HU daily for 6 months and then 90 mcg Pegasys weekly for 6 months. I have a long way to go to get my jak2 below 10, but at least I am headed in the right direction.

[JT_Marlin in reply to Flynn2107]

Great news Flynn!

[Flynn2107 in reply to JT_Marlin]

Thank you

[EPguy in reply to Flynn2107]

As you may have seen in posts here, your results at 2 years will be most interesting since the trend takes time. I've posted this chart before, it shows that, on average, at 6 months, the reduction is still much to go. Of course this does not reflect specific persons.

ncbi.nlm.nih.gov/pmc/articl...

PEG 7+ year study

[Manouche in reply to EPguy]

« In the model, the number of malignant stem cell vanishes at year 12 for the patient shown in Figure 8. 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.

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

[EPguy in reply to Manouche]

I checked out this study again. It's intended to validate a prediction model for INF patients. It's hard to read in one bite and lots to see in there.

I think the above is a mathematical prediction for a good responding specific patient in Fig. 8 of the study. The study points to better prediction results with the better responders.

<<good responders generally appear to calibrate better to data than poor responders>>

The model << may predict how long treatment has to be continued for good responders.>> That is useful.

I think the PEG study of the plot "7+ years" I showed above is more of a population average. We discussed in earlier posts.

--

A separate finding:

-In this study Pegasys worked better than Pegintron, might this be relevant to Besremi?

We discussed a bit before on this, but rereading I get more out of it now:

Diffs between Pegasys and Pegintron. This is the only study I know that tries to compare them directly in MPN.

<<Pegasys performs better than PegIntron.>> Lower Fig. 1 shows this.

Possible reason relates to the PEG process: <<PegIntron is more likely to hydrolyze due to an unstable urethane bond between the pegylated portion and the recombinant IFN molecule compared to Pegasys, which has a more stable amide bond. Therefore, Pegasys has a longer half-life and prolonged plasma concentration compared to PegIntron>>

This last sentence could almost read from Besremi's marketing vs Pegasys, suggesting continued improvement from Intron to PEG to Bes. The pattern is reducing the number of pegylation sites and controlling their positions. Bes generally has just one such well controlled site vs multi and variable sites on the other INFs

Intron's lower tolerance affected dose size: << treatment-related toxicity was higher among patients treated with PegIntron compared with Pegasys after 36 months of treatment. Hence, the patients randomized to PegIntron received lower doses compared to Pegasys, which may have resulted in a lower molecular efficacy>>

Besremi has its improvements in the pegylation process discussed here, so maybe it allows higher dosing and better results. There is a current thread where we are discussing dosing for INF.

[Flynn2107]

Thanks for your reply, very helpful information.

[IrishSarah]

Thanks for sharing your good news!