Besremi Trial update

[CLake4]

Apologies for the long post. I have learned so much from this site so I would like to share my experiences on the Besremi trial at MD Anderson in Houston, Texas for those who it might help.

I am a 58-year-old female with no other health conditions. I was originally diagnosed in 2014 with ET but progressed to PV in 2018. I am now 9 months into the Besremi trial. I started on February 20th, 2024, with the first dose of Besremi of 100mcg. I increased 50 mcg every two weeks until reaching 500mcg on June 11th. For the first six months they monitored heart, kidney, liver and thyroid function every two weeks in addition to a full CBC. After 6 months, they are monitoring vital organs only once a month but continue CBC bi-weekly. It is a lot of blood draws.

At the low dosage, my symptoms were diarrhea and cramps. As dosage increased, I acquired neuropathy that required low dosage of Gabapentin. At 500mcg I experienced hair loss, dry eyes, acne, sore gums, UTI, and bone pain. The bone pain could be severe, but I was able to manage with Tylenol. I had five phlebotomies during the first 6 months of the trial, which is more than I have ever had in any year. (I started therapeutic phlebotomy in 2018). I was told that hematocrit responds more slowly and would “fight back”. My WBC and Platelets responded early and dropped quickly. Side effects definitely escalated on the high dosage.

After six weeks at the high dosage, in September, my hematocrit finally responded by dropping to 39 from level of 46! Also, as I was experiencing high liver enzymes, dosage was reduced to 350mcg biweekly. By this time my WBC declined to 8.2 k/ul from 19; and Platelets are now 480 k/ul from 1,199.

It was much needed relief at the lower dosage of 350 mcg bi-weekly and most side effects resolved except for slight diarrhea within the first few days after the shot. I also have mild nightly neuropathy, for which I continue to take 300mg Gabapentin before bed.

Even though the trial targets 500 mcg bi-weekly, I am told everyone is different and they find the max level that each person can tolerate. The goal is to stay at the max level tolerated until hematocrit remains stable at a targeted 40. Sadly my hematocrit continues to climb each visit in the last few visits, so they will not be able to reduce my dosage until that stabilizes. Once stable, the goal is to reduce to one shot monthly at a low dosage.

I will not deny that at the 500mcg bi-weekly, it was miserable. But at my current dosage my side effects are not worse than my original issues- headaches, dizziness, nose bleeds, muscle aches and fatigue. So at this point, I would say I am happy with the results and very grateful to be so well monitored.

[hunter5582]

Thank you for your participation in the clinical trial. The science will not move forward without people willing to participate in these trials. Your experience is a good example that the maximum dose of Besremi is not tolerable nor desirable for everyone. We are indeed each different in how we respond and how much of any medication we can tolerate. My maximum tolerable dose is 175mcg due to lymphopenia and neutropenia. I also experienced an elevation in LFTs to 3X/ULN. Fortunately, the LFTS returned to an acceptable level with a daily dose of Milk Thistle Extract.

Thank you for sharing your experience in detail. That is very informative and helpful. I am curious as to why the HCT target is 40%. The convention is 45% for males. Some MPN experts use the same target for females while others use 42/43% for females.

Wishing you all the best and success moving forward.

[EPguy]

Quite a journey. What particular neuropathy have you acquired on Bes?

As Hunter notes, 40 is lower than the required HCT range, and an IFN dose to get there will be higher than needed for the usual HCT goal.

[Roxanne22]

Thank you CLake4, it's interesting to read your post and shows that you will probably fare much better on a lower regular dose. I have showed signs of sensitivites to medicines in the past, allergic responses etc, so for this reason they have started me at only 50mcg per two weeks. I am due my 2nd injection today. Thank you for bravely entering the trial and wishing you well in finding your optimum level of dose to maximise your health and vitality. Sending you love and best wishes. Sarah

[Meatloaf9]

Thank you for participating in this trial. I don't understand why they did not cut the dose back from 500 immediately when you had all of those adverse effects, I guess that was part of the trial that a rigid dosing schedule was followed to map side effects?

Hoping you get the desired result and that besremi works for you long term. Best to you always. Keep us informed please.

[CLake4 in reply to Meatloaf9]

To be fair, they reduced it as soon as I complained. Side effects at high dose took a few months to accumulate.. they were not immediately difficult.