Besremi Allele Result

[EPguy]

My Dr recently ordered a Jak2 allele test. This is 6 months after starting Bes. I think there are few Bes patients outside trials with allele data result so it's interesting. Current dose is 140, allele results are from less than 140.

Result is reduction from 14% to 10%. This is of course very nice. I told Dr that my info has reductions from already low levels being harder to get than from higher levels. He agreed and is also quite pleased and even maybe surprised. He agreed we could not even have this discussion a few short years ago.

This may be related to discussions we've had on the forum that Homozygous Jak2 (associated with alleles over 50%) being more responsive on avg to IFN than Heterozygous (associated with lower alleles)

I was quite stressed anticipating this result, and didn't tell my husband about it till after. But he sensed something up from the short 3 week appointment schedule and has been way more stressed than I.

The 14% is from near Dx 1-1/2 years ago from a blood test value. I also have a BMB value of 19%. But Dr says, quite reasonably, we will compare only the same type. He says this 10% reading is very accurate and reliable. I might guess the BMB is now at 15% but have no results to actually know.

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The plot here is from

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

and I added my result as the short black line. This is the most relevant plot I can find to compare with. This 7 year study started with super high PEG doses (450/week vs my start at 50/2 weeks for Bes) which might explain the shallower starting slope of my line (and might not) They finally settled on 90/week for that trial. Note the result in this study gets interesting at 5+ years, the Ropeg study has this 5+ year data but they are not telling.

This big question in my case of course is whether slope keeps going. I think he plans alleles every 6 months as seems common in trials

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It is possible the NAC supplement I take is helping. I can say for certain that NAC has not precluded an allele reduction since there was one. If I were a mouse NAC was shown to reduce allele if allele starts under 100%. Another study with 100% VAF mice did not get allele reductions which is consistent with how IFN works (see recent post).

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CBC is also very good:

HCT- 40.5 (Min= 40.1, this is getting too good and maybe I'd feel better with a bit more)

Hb- 14.3

Both HCT and Hb are lowest ever

PLT- steady at 250

Neut-1.95 (Range 1.56-6.13)

Lymph- 1.08L but recently rising (range 1.18-3.47)

The "ones that don't matter" (MCV etc) all in range, HU takes these way out, and Dr said they would not fully normalize on IFN. They have normalized.

- My QoL has been tolerable lately, we're taking a long trip so I will really find out soon.

CMP count was all good, except chloride was well over range, 110, range 96-106. I've always been high here but this is higher. This can be from dehydration, which I was quite hot on the walk to Dr. Hope it gets back just regular high next CMP.

[Cja1956]

Wonderful news! Looks like the Besremi is working.

[Lena70]

Fantastic.

[Hopetohelp]

very pleased to hear the results and very encouraging

[Miriammusic]

Tbrilled for you! Now that I am off the Bomedemstat, I am going to begin Besremi. I had an appointment with Dr. Mesa and I’ll begin on 50 mcg. Just received the syringes.

[Aneliv9 in reply to Miriammusic]

Where you on the trial of bomedemstat? Why did you quit?

[Miriammusic in reply to Aneliv9]

Yes, I was. I believe I posted about it several times here so you can check the archive. 😊I quit because I couldn't find the sweet spot between a dosage that would bring my counts under control and dosage that would not cause me side effects that I couldn't handle well.

[EPguy in reply to Miriammusic]

I just made a reference in a post to your Bom experience. Look fwd to your good results on Bes.

Usually Bes starts at 100 if you're not switching from HU. But you're with near #1 in the business, it will be good to hear what his plan is. We saw in the member survey post that many here need only quite low doses for get CHR.

Dr. Mesa might have access to a big question I've had, and we all have an interest in: what happened to this plot red line after the 60 months they stop at. They have published 6+ year data but are not releasing this part of it.

Ropeg5+Years

[Manouche in reply to EPguy]

 »Dr. Mesa might have access to a big question I've had, and we all have an interest in: what happened to this plot red line after the 60 months they stop at. They have published 6+ year data but are not releasing this part of it »

The data will be released next year. No doubt about that. IFN keeps working even after 10-20 years. Less people seem to tolerate it over the years, but it keeps working on the jak2 clone.

[EPguy in reply to Manouche]

Look fwd to the release. My interest in 6+ years has been esp driven by the green and blue lines in the plot at top here. In this result we need CMR for durable molecular response. The Ropeg plot I think is an avg of all MRs.

On the long term tolerance, we can hope the modern Peg'd types and careful dosing can increase tolerance.

[Miriammusic in reply to EPguy]

Dr. Mesa is not my hematologist, but I was fortunate enough to have an appointment with him. Both he and my regular hemo/onco agree on the 50-mcg dosage. I am just very sensitive to meds I guess. We will see what happens.

[EPguy in reply to Miriammusic]

You may have seen this plot from forum members. It shows a large portion with good response on quite low doses. My Dr said in trials they almost always dose high because a "preference for success" while clinical practice trends lower.

But my Dr keeps wanting to increase it. I believe my sweet spot is 120mcg. But Manouche has noted some info pointing to higher odds of CMR with higher doses.

BesDoseMPNVoice

[ritaandscooter1 in reply to Miriammusic]

Hi, please keep us posted on how you do on a 50mcg dose. Like you I'm really sensitive to meds. Was on low dose PEG but my liver enzymes shot through the roof fairly rapidly and other side effects were not good. I'd be interested in how you do on Ropeg with this low dose. Thanks Kerry

[Manouche]

 »This big question in my case of course is whether slope keeps going ».

It will, no question about that! (unless you have to modify the dose or temporarily stop for some reasons). You’re heading towards a complete response within the next 3-6 years and that’s a great news 👍🏻

[EPguy in reply to Manouche]

I agree from the look of the plot I used for comparison it seems promising. My impression is we can have a good idea of the end point by the 2nd year. But one report does have CMR after longer than that.

I'm having a somewhat off day again, maybe if it gets near zero there will be fewer of these.

[Manouche in reply to EPguy]

Whatever the results next year, you’re already ahead of schedule !

JAK2 at 60 months

[EPguy in reply to Manouche]

This looks like an updated version of the chart here. Your updated one has even stronger correlation of MR to CHR, essentially saying without CHR, MR is unlikely.

It's not clear why these are different, both are at 5 years.

Early Version ContiPV

[Manouche in reply to EPguy]

Without CHR, MR is less likely but possible. We’ve seen it on this forum.

[Emmyroos]

Awesome!! That's a great reduction in AB! You must be stoked.

[EPguy in reply to Emmyroos]

I was yesterday, today there's clouds of malaise. Tomorrow, who knows.

But it's quite satisfying vs my 1st Hem who said my allele will near certainly increase over time (pre-IFN thinking)

I think we'll see plenty of other members with allele progress on Bes as more get tested. My Dx is PV, but I have some ET features, so it's possible there will be similar results for some in the SURPASS-ET trial.

pubmed.ncbi.nlm.nih.gov/359...

[mhos61]

Really pleased for you, those numbers are perfect. I hope you manage to enjoy your long haul trip too.

[EPguy in reply to mhos61]

I agree, couldn't ask for more, except a clear head.

We should enjoy our long haul trip way more than our long haul Covid.

[Barbiebreath]

That’s great news and so encouraging. Thank you for sharing.

[Solyesh]

Overall great news! Hope the slope and numbers continue!

[Jamesxyz]

Wow, that's an amazing result.

What about liver enzymes, are they normal now?

Any side effec ts from the injections?

[EPguy in reply to Jamesxyz]

CMPs have been stable and mostly center of range since Dx, HU and now IFN. AST is up slightly last test, 47, range 13-62. NAC may be helpful for liver based on info I've read. Kidney GFR is improving a lot currently at 76

One CMP that is quite high is chloride at 110. I've always been high here, but this is highest so far. I've read it can be dehydration or kidney.

I have no troubles at the injection site, I think Bes is usually good on this, except the last one I used the needle that comes with it and it was dull, hurt a lot. My Dr's ones are way better.

Longer term, I do get weakness from the IFN. Muscle tone is declining some. Also get malaise, my worst symptom in general. Wake up time often feels really bad. On dose of 120 I had two full weeks of feeling ok, at 140 not so.

[Jamesxyz in reply to EPguy]

It's good to hear how well you're doing, congrats.

I'm considering the switch to besremi, hence all the questions.

You mentioned Dr's needles, were you getting the injections on an outpatient basis?

[EPguy in reply to Jamesxyz]

I did and do at home. But Dr offered needles, and now I get my supply there.

All's good except symptom burden, but I've had trouble there from Dx.

If you qualify for IFN, it does seem worth the switch to me. HU didn't affect my energy level as much as Bes does but HU's well known side effects were an issue for me.

We're both older than the old fashioned guidelines for getting IFN, but this limit is no longer as common a practice.

[Jamesxyz in reply to EPguy]

I'm 74, what is your age?

The hydrea controls my counts perfectly with a low dose (1 pill daily).

No side effects, I don't even know I'm taking it.

However I am intriqued by the remission possibilities of besremi.

My Dr will precribe it, however because of my age, he is not sure it will benefit me.

The other negative is the cost.

[EPguy in reply to Jamesxyz]

I'm 63, 61 at Dx. I'd like to add that to my profile but can't figure out that procedure.

If you're feeling and doing well on HU that does reduce motivation to switch. I've never felt good for long periods on anything since Dx (and concurrently with long covid)

There's also a recent thread that shows HU can provide reversal of marrow pathologies for some. I'm not sure on this one but I will discuss with my Dr. If true it does give HU a better context.

healthunlocked.com/mpnvoice...

[GardNerd]

This is great to see. Thanks, as always, for sharing such great information — about your journey and information that helps the rest of us, too.

[EPguy in reply to GardNerd]

Glad to help, I do try to post things that add info for others if I can.