Update 8.0 - Next chapter

[hunter5582]

As you may remember from previous posts, my HCT has been creeping steadily up. It looked initially like 175mcg Besremi was going to work, but the last two CBCs done outside of my hematology office indicate otherwise.

02/22/24 HGB=14.6, HCT=45.6, NEUT=1.19, LYMPH=0.73

03/19/24 HGB=15.5, HCT=47.3, NEUT=0.99, LYMPH=0.69

With NEUT<1.00, it is not viable to increase the Besremi dose. Per the previous plan I made with my MPN care team, I will arrange for a therapeutic phlebotomy. This will be the first phlebotomy since January 2023 and only the second phlebotomy since I started on the IFNs in May 2021. I consider that an acceptable response, though I would prefer to be phlebotomy-free. This is an example of where we must make rational risk/benefit decisions when managing an MPN. While I would prefer to increase the Besremi dose, it would not be in my best interests.

I am planning to keep the Besremi dose at 175mcg unless my MPN care team advises otherwise. I expect we will give it a bit of time to see if the NEUT comes back up above 1.00. If necessary, we will drop the dose back down to 150mcg. My primary treatment goal is to ensure quality of life as I define it. This approach is the best way to ensure that outcome.

The last A1C, glucose results indicate prediabetes may be progressing. These are the highest numbers I have had, though I have hovered above and below the limit for prediabetes for 10 years.

10/05/23 A1C=5.9, GLUC=123 (A1C Ref Range = 4.6-5.6)

02/22/24 A1C=5.5, GLUC=111.2

03/19/24 A1C=5.7, GLUC=117

Numbers have reduced slightly, but still higher than they have ever been. I do not believe this is related to Besremi due to my history prior to starting on the IFNs. I had my annual appointment with the endocrinologist in February. He does not advise any action other than healthy diet, exercise, and continue with weight loss. I have lost about 5 pounds in the last month, so that is moving in the right direction. I will meet with my PCP next week to review the plan.

In somewhat better news, I met with my cardiologist. I have had no incidents of tachycardia since June 2023. I am very pleased about that. Hopefully that trend will continue. As an interesting side note, the cardiologist agrees that systemic inflammation (from JAK2/NF1 mutations) plays a role in cardiovascular and other medical issues.

The only other news is that I succeeded in getting the Durolane injections into my knees. It took a bit to access the treatment through Medicare, but persistence overcame resistance. I am back up to full speed and able to exercise without problems.

That is all for now. A few more interesting health learning opportunities and on the whole success managing the PV and other health conditions. I am blessed to have an excellent care team to help manage everything. They listen to their patients and respect the patient’s ability to make decisions about their own care. They provide many outstanding examples of how shared decision-making works.

Wishing all of you all the best and success on your journeys.

[C_Anne_Orange]

Thank you Hunter for your detailed post. It is so helpful to follow your journey and to hear your progress and rationale. I always learn from your stories with this variable, challenging, rare MPN experience. You seem so adept at managing all of the competing factors and making good balanced decisions. Another round of good progress in maintaining your health and quality of life! Thank you!

[Ovidess]

And good luck to you on your treatment journey as well! Thank you for sharing so much of your time with this forum.

[EPguy]

The WBC limitation is familiar, my Dr stopped raising my dose for that reason (before I got knocked off)

You seem to fit the criteria for the Rusfertide trial, but even if you wanted to try, I don't think they have any near you.

I agree on the A1c, in my case it had no effect from Bes.

Wishing you all that continuing QoL.

[hunter5582 in reply to EPguy]

When I last checked on the Rusfertide trial, it required needing phlebotomies more often than I have been needing them. The Phase 3 trial criteria include - At least 3 phlebotomies due to inadequate hematocrit control in 6 months before randomization or at least 5 phlebotomies due to inadequate hematocrit control in 1 year before randomization.

I will be interested to see is intermittent use of rusfertide becomes an option for people on other therapies. I would be interested in using this as an alternative to phlebotomies if it is a viable option.

Thanks for the input.

[EPguy in reply to hunter5582]

That is an important detail, a phleb about every two months.

With the trial design allowing other therapies, it looks like they want it approved at least in part as an add-on to those other therapies.

[Na56 in reply to EPguy]

I hope all goes well for you Hunter. Thank you for all the support you give to us. All the best to you Irene

[Loooonglife]

Thank you for sharing your particular situation. We all can learn from it. For the last 18 months until this January my HCT has been well controlled (<45) on 130ug Besremi every 14-17days. Recently, and similar to you my HCT had been increasing to 46.8, while lymphocytes and neutrophils remained at or below the lower limit. Iron levels were in the normal range, which we tested before receiving a phlebotomy, which I tolerated so much better than in the past. My HCT dropped to 40.8 within a couple of weeks.

My hematologist also requested to check for changes in the JAK2V617F allele frequency, and general mutational status. I am currently waiting for the results and will let you know if any significant changes are being detected.

[Kelly2 in reply to Loooonglife]

Hi. How do you check for the changes?

[hunter5582 in reply to Kelly2]

There are different types of genetic tests for MPNs. One is the JAK2 variant allele frequency which can be checked with a JAK2 Quantitative Analysis. There are also genetic tests that check for a wider range of mutations, including all three driver mutations and known non-driver mutations. This is one example. labcorp.com/assets-media/2673

[Jull2002]

Great to hear you're back to exercising. "..persistence overcame resistance", well said.

[Strumin210]

Greetings hunter 5582 from the Deep South close to Florida and Georgia. I was talking to my GP doctor yesterday and also I questioned him about other numbers in my current CBC. My nurse practioner at the Oncology office didn't mention my other numbers that are currently high or some that are low such as lymph, baso,and high such as RDW.He said nothing to be concerned about. I do believe I have a good Oncology doctor. One of my questions is the Doctor's nurse nor the Doctor herself have never done a physical exam. My GP said yesterday that all his patients said the same thing. If you have an enlarged spleen or liver due to the platelets being so high. Would it not be a exam that would determine that? Sorry for letting the reply steer toward me. I pray that all goes well with you and have a great quality of life.

[hunter5582 in reply to Strumin210]

Asking questions is what the forum is for.

Checking spleen and liver size by palpation is a part of a routine assessment for any MPN, at least initially. This is sometimes accompanied by imaging. The oncologist may not check every time once you have established a baseline that splenomegaly is not an issue.

Depending on what your condition and treatment are, some of the abnormalities on the CBC are expected and not necessarily a concern. My RDW (Red Cell Width Distribution) is always high. It is common for the leukocytes to be low on cytoreductive treatments. That is OK provided they do not get too low.

If you want to know more about the meaning of your CBC or any other lab then be sure to ask your provider. They can give the best case-specific explanation. It helps to understand the basics of reading a CBC. This video gives an excellent explanation.

youtube.com/watch?v=Xj_yE1p...(Not working as expected?)

[MaggieSylvie in reply to hunter5582]

Thanks, Hunter. Gosh that was very clear. I will have to watch it again with my blood redouts beside me.

[Whitehair51 in reply to Strumin210]

At my last appointment with my hematologist, he did an exam of my spleen, even though my platelet count was normal.

[DiveGoddess]

Good Morning Hunter,

By taking the time to list your lab and explain plan, you help us all to be better stewards of our own health. Thanks for your continued dedication to this group. Sounds like you keep a complicated situation manageable. Having faith you will continue to thrive, best of Luck in your Journey 😊. Christy

[Mostew]

may your book have as many chapters as War and Peace.

And the battle continue to be peaceful….

Best wishes to you

[dladydi]

Keep up the good fight Hunter. Once again thanks for your gift of information for all of us who are also navigating this condition.

[GardNerd]

Thanks for this update and for sharing your journey and the rationale for managing things effectively. The way you own everything and actively participate in your treatment is a great example for all of us.

[sbs_patient]

Hunter, thanks for sharing your results. I'm really sorry to hear that you've had to return to therapeutic phlebotomy. Best of luck as your journey progresses.

Steve

[DougyW]

Here's hoping everything goes well for you Hunter. 1 phlebotomy in 14 months is a pretty good outcome. Keep battling on and know we are with you.

[Paul123456]

Hi Hunter

Do you have regular BMBs/spleen checks? I am also on the Neut edge (of 1) but the Pegasys appears to be slowing, if not slightly reversing, progression so a risk worth taking.

My lymphocytes are c. 0.4 but my immunoglobulins are good so I assume I’m sourcing some from the lymph nodes

I’ve been trying to fix on the Goldilocks dosage for over three years but been averaging Neuts at just over 1. I wouldn’t regularly want to go below 1 but an acceptable risk if controlling my MPN-U

Best Paul

[hunter5582 in reply to Paul123456]

I do not do routine spleen checks anymore. I did have very mild splenomegaly which was noted as an incidental finding on imaging for other purposes. It actually reduced a little over the course of a couple of years. I get poked, prodded and scanned enough for multiple reasons that I am sure any enlargement would get noticed before I ever had splenomegaly symptoms.

The Goldilocks dose can be a moving target as the MPN evolves over time. It is always a balancing act between the risks/adverse effects and the benefits of the medications. I appear to be at my maximum dose at 175mcg Besremi. If I need to do an occasional phlebotomy then so be it. i will find the new right balance in due time.

Wishing you all the best.

[Pounds11]

I gain courage from your calm and intelligent posts. Hopefully the rare phlebotomy will set the course again. You are a gem. Thank you for your words. Marti

[Hidden]

Thank you for always being there for us, Hunter. All the very best for you in your next steps.

[gilded]

Thanks so much Hunter for sharing. Your candour is greatly appreciated since one learns so much. May the force be with you.

[Mishie14]

Thank you for sharing your journey! I very much appreciate learning from you and having ‘persistence overcame resistance’ is awesome! Love it. Wishing you continued success in managing your health.

[lizzziep]

Hope all goes well for you!

[Lyndjs]

Thank you for sharing your update, your journey, and all your experiences, Hunter. I hope all goes well for you and you feel the benefit from the venesection and the injections in your knees.

I'd also like to thank you, for being a part of our care team, as I'm sure, I'm not alone in reading your posts and feeling more informed about PV and thus, better able to engage in consultations.

🐣Happy Easter x

[JP1952]

Ditto the above post by Lyndjs.

[ainslie]

that all sounds pretty reasonable, one venisect a year or so is pretty common even when on meds.

I was interested to read what your cardiologist said re inflammation from Jak2 can cause heart issues. Is that inflammation shown in any of your markers.? I was amazed to be diag recently with Premature Ventricular Beats and Atrial fibrillation, my CRP is low and everything else is good and Jak 2 is 20%, interesting your cardiologist knew about that, certainly in the UK haems know little about cardiology and cardiology know little about haematology.

[hunter5582 in reply to ainslie]

I have shown elevations in IL-10 (anti-inflammatory cytokine), cortisol, and TGFβ. This indicates that my body is responding to the presence of inflammation. What is interesting is that the usual inflammatory cytokines, TNF-α, IL-1, and IL-6 were not elevated. There are, of course, many other inflammatory agents in the body. I had hoped to find an objective marker to measure response to anti-inflammatory intervention. While there likely is something, it is not worth the time and expense to find what it is. While it is subjective, the level of pain I feel from osteoarthritis/tendonitis is the measure that I am using. While these are not the only systemic inflammation symptom I experience, the pain is easy to assess and has significant impact on my quality of life.

Doctors here in the USA have varying awareness of systemic inflammation and the body as an integrated system. My Integrative medicine doc is keenly aware of it and she is the doctor I consult with this issue directly. The MPN Specialist is also aware of it and it is an area of interest for her. I am fortunate to have an experienced and well informed cardiologist who understands that the heart is connected to the rest of the body and does not function in isolation. We had an interesting conversation about the factors that affect blood pressure like insomnia and how systemic inflammation has wide ranging impacts on sleep and other issues.

Wishing you all the best.

[Luthorville]

Is it worth trying a higher dose to see if it does indeed push net lower? Even if that’s likely it may not be certain. If it does decline you could simply reduce your dose.

[hunter5582 in reply to Luthorville]

The recommendation from my MPN care team is to not let the NEUT drop below 1.00. I agree with this plan as I do not want to experience too much suppression of my immune system. Each increase in my dose has Besremi has further depressed the leukocytes, so I would anticipate the same would happen if i increase again. I believe it is in my best interests to use the occasional venesection to reduce the erythrocytosis rather than compromise my immune system too much. I expect that I will tolerate the reduction in iron levels well providing the levels do not drop as low as they did in the past when I was using regular venesections.

All the best.

[KLCTJC]

thanks for the update! And thanks for answering my questions about the wbcs. Will see if I can stay at current dose or have to decrease in a few weeks. Sounds overall you are still doing well, which is great!!!

[Spanelmad]

Glad your persistence worked!!Hoping I can convince my GP to redo my knees

[rmfisch]

thanks for the update hunter5582. We all learn from your experience and insight. All the best.

[Aldebaran25]

It is always interesting to read your posts Hunter, thank you for this update, it is much appreciated. I am also having some trouble lately keeping the hct under the target with Pegasys and have needed two venesections since January. In a couple of days I will be having extensive blood testing since I have moved countries and am now under a new team. Well, it looks promising as they seem very thorough. They mentioned moving me to Besremi as Pegasys is not available here for the PV indication. Can't wait to see the results of all those tests although I may regret saying this :))... Be well and thank you again!

[hunter5582 in reply to Aldebaran25]

I did not find much of a difference between PEG and BES. Theoretically, BES is supposed to be easier to tolerate. I expect it will prove that this, like most else, is an individual response issue.

Wishing you success with your new team and new plan.

[Paraic2021 in reply to hunter5582]

Hunter may the intercession of Jesus Mary and Joseph keep you safe you are in inspiration to many

[artydutch]

Thanks for sharing. You are so knowledgeable that you know what interventions needs doing before your doctors even suggest these. I hope all will pan out as you figured it might.

I am glad you have such a good team of doctors.

Thanks for all your good advice that you give to all on this forum!

[hunter5582 in reply to artydutch]

Thank you for the kind words. I am blessed to have a wonderful care team.

This is a situation we had planned for. I had recently discussed the options should I continue to see escalation in the erythrocytosis. The options to either use venesection or an increase in Besremi was premised on the level of leukopenia. The decision was quite clear based on NEUT<1.00. It is just a matter of executing the plan. I will go in for the venesection next week, Tuesday 03/26. I will do a follow up lab on Thursday 03/28 to see where I am at. The next lab is scheduled for April 26. If things go as they did last time, my HCT will drop to target for at least a year. We will see how it goes.

All the best.

[ETMF]

Wow Hunter, very descriptive and factual. I would think that you will be able to stop the diabetes that has its sight on you. Praying and desiring the best outcome. I enjoyed reading that your team allows you to have a voice in your situation.

[hunter5582 in reply to ETMF]

Thanks. I am hopeful at moving the prediabetes in the right direction.

Regarding shared decision making, this is the proper way for medicine to be practiced. Doctors listen, educate, consult, advise and write orders, but do not decide for the patient. The patient is the only one who can decide what the course of treatment will be. Ideally, this decision gets made in the context of a collaborative relationship where there is mutual respect. Shared decision making based on meeting the patient's treatment goals results in the best outcomes.

We have both the right and the responsibility to ensure that shared decision making occurs. Wishing this outcome for all.

[JustKeepSw1mming]

Hi Hunter,

Thank you very much for sharing your results.

I agree with the many others here. Your posts are so informative. They really help me understand my condition better.

You are an insperation!

Thank you and wishing you all the best.

Take care.

Mary

[Cassandra61]

Thank you Hunter for so generous with your time and attention, we all benefit so much from you. Wishing you the very best.

[mother2britton]

Thank you for sharing. Stay well.

[conno61]

Best of luck on your journey Hunter.

[johoho]

Hi Hunter, I always read your posts with interest, I have read back on your profile and find you have previously not tolerated HU and began Peg before moving to Besremi. I'm in the UK and began Peg in November 23 for PV. Previously I was Aspirin and phlebotomy once/twice a year only. Starting meds came as a result of my enlarged spleen and I've injected 45 peg since November. Since the start, my Haem and nurse have been keen for me to try Ruxolitnib as it's more likely to help the spleen, but I'm worried about it's impact on my anaemia. You sound as though you are sticking with Besremi for now, would you consider Rux?

[hunter5582 in reply to johoho]

I would definitely consider ruxolitinib if my MPN profile indicated it may be a better choice. The more recent evidence that RUX may reduce the JAK2 allele burden is very hopeful. While both medications can help reduce splenomegaly, ruxolitinib is likely more effective for this purpose.

You mention having both anemia and PV. PV commonly causes low iron, using it up to make too many RBCs. Anemia is a deficiency in hemoglobin/red blood cells. It is not the same thing as iron deficiency. The purpose of the phlebotomies is to further reduce the iron levels to control the erythrocytosis. Less iron = fewer RBCs. The goal is to induce chronic iron deficiency without anemia. Unfortunately, chronic iron deficiency without anemia can have adverse effects. These adverse effects were the reason I started on the IFNs. I feel much better now that my iron levels are higher.

In weighing this decision, you will need to be clear about your treatment goals and risk tolerance. Which medication lines up best with the risks/adverse effects being worth taking to meet your treatment goals. How significant is your splenomegaly? Is the PEG having a positive impact on this issue? You know how you react to PEG but not to RUX. Does the potential improved reduction in splenomegaly justify making the change?

This decision is a judgement call. Both medication are viable choices. I would certainly consider a change if the splenomegaly was a primary concern.

Please do let us know what you decide and how you get on.