« The myeloproliferative neoplasms (MPNs) are chronic blood cancers characterized by elevated blood cell counts and, after decades, the development of bone marrow failure. Blood clots are common and contribute massively to the symptom burden. Treatment with interferon (IFN) alpha-2 normalizes elevated blood cell counts within weeks to months. This treatment has been used off-label over the last 30 years. Today, a novel interferon alpha-2b formulation (Besremi) is marketed for treatment of the MPN disease polycythemia vera. Another IFN formulation is interferon beta (IFN-β), which has been used for decades in the treatment of multiple sclerosis. Several studies have shown IFN-β to possess stronger anticancer capabilities than IFN alpha-2. However, only a few cancer trials have been conducted, none in patients with MPNs. In this paper, the rationales and perspectives for using IFN-β in patients with MPNs are described, and future research directions are outlined for investigating the safety and efficacy of IFN-β in MPNs »
« …Based on 30 years of experience with rIFN-α2 in the treatment of MPNs, showing the safety and efficacy and the recent marketing of the first rIFN-α2b formulation (Besremi) for use in the treatment of newly diagnosed PV patients, we can conclude that stem-cell- targeted therapy with rIFN-α2 will be the cornerstone in the future treatment of MPN patients. Unfortunately, a large number of patients do not tolerate rIFN-α2 or are refractory to treatment. The novel rIFN-α2b Besremi seems to be less toxic and perhaps also more effective than treatment with Pegasys, which is the only alternative today. Therefore, we are in an urgent need of stem-cell-targeting drugs other than Besremi and Pegasys, whether as monotherapies or in combination with agents that target the concurrent chronic inflammatory state, which is considered to be of major importance as the driving force for clonal expansion and evolution in the biological MPN continuum from early cancer stages (i.e., ET and PV) to the advanced myelofibrosis stage. Accordingly, studies on the safety and efficacy of pegylated IFN-β (e.g., Plegridy) are urgently needed, the optimal design being a randomized pilot study between pegylated rIFN-α2 (e.g., Pegasys or Besremi) and rIFN-β, with comparisons of safety, efficacy, and toxicity profiles and concurrent molecular and immune cell studies (i.e., frequencies, distribution, and functionality) before and during treatment. Studies of the safety and efficacy of rIFN-β in patients who are refractory or intolerant to rIFN-α2 might be highly important to determine whether rIFN-β might “rescue“ such patients. Studies of rIFN-β in the CHIP-JAK2V617F stage before the overt development of MPNs might also be highly relevant to assess whether rIFN-α2 or rIFN-β might reduce or potentially eradicate the malignant clone in the earliest stages of MPN development [54]. If studies of monotherapy with rIFN-β show similar or even superior safety and efficacy as compared to Besremi or Pegasys, the path is open for studies of the safety and efficacy of the combination therapies mentioned above, and possibly others as well (e.g., hydroxyurea, statins, and colchicine) [54]. Studies on the safety and efficacy of anti-CALR monoclonal antibody therapy are in the pipeline; as part of this research program, it might be tempting to conjugate with rIFN-α2 or rIFN-β. This strategy has been considered for years but has only recently been accomplished in the treatment of multiple myeloma. Lastly, in the COVID-19 era, it is important to underscore that several studies have shown rIFN-β to have a favorable impact on the clinical course of COVID-19. The rationales and evidence for using rIFN-β as monotherapy or in combination with ruxolitinib have most recently been thoroughly described… »
They use an incomplete comparison for IFN-a "However, as alluded to above, a dropout rate of up to 40–50% was recorded in the DALIAH trial during long-term treatment with Pegasys or PegIntron" The Bes trials had far better results so the bar is higher.
" rIFN-β has been used for decades in the treatment of multiple sclerosis (MS), with an excellent safety and efficacy profile" so there should be fewer safety worries in MPN trials.
rIFN-β is missing in studies:", the therapeutic potential of rIFN-α in the treatment of cancers has been investigated in 248 trials, whereas the role of rIFN-β as an anticancer agent has only been investigated in 7 trial"
We're in the IFN revival era "interest in using rIFN-α2 in MPNs has been revived in recent years" due to the mounting evidence from several studies within the last 5–10 years"
Early troubles with non-peg IFN-a discouraged research into other IFNs.
rIFN-β is way better at attaching to its target: "the binding affinity of rIFN-β to the interferon receptor (IFNAR) is much stronger than that of rIFN-α (50-fold for IFNAR1 and 1000-fold for IFNAR2)"
"there are reasons to believe that the treatment of MPN patients with IFN-β may have advantage: "IFN-β may not only have the potential to normoregulate elevated blood cell counts, but also dampen the chronic inflammatory state that accompanies MPNs and likely contributes to clonal expansion and evolution."
For a different cancer: " early studies in breast cancer cell lines showed IFN-β to be highly superior to IFN-α;..."
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I presently have a huge interest in this, with my ongoing very adverse neurological vax reaction:
"The potential of rIFN-β in the treatment of neuroinflammatory diseases other than MS"
the drop out rate with long term use at 40-50% is in line with what Dr Hasselbalch told me, I wonder when we read about 20% of Peg users getting some sort of remission/ CMR is that 20% of the remaining 50-60% of those who can tolerate it long term or 20% of the original start group 100%
I am the one EPguy responded too. As I found out I have a benign form of MS. So, MD Anderson doc didn’t want to start Besremi. I have found articles proving that INFa can improve MS. But I have looked at many articles on INF b and to me it seems that it has the same potential with less side effects. Right now I am on nothing until I see MD Anderson doctor in less than 2 weeks. My decision will be made after I see him but I have decided if he says no to Besremi I will contact neurologist and say let’s start INF b. I have plans to give my MD Anderson doctor a heads up on my plans. I want to see what he says about INF b. So, I am so happy to see this post because I have at least one article proving my diseases are related. Luckily I have no symptoms of either disease. But I will keep y’all posted. As this may help a lot of people. I know INF b is used in adjunct cancer treatment of breast and liver cancer. I would love to see them study this!
In a prior post you said FNa was bad for PV per MD Anderson. But you found reports that say otherwise. Does MDA have data to support the contra indication?
I'm having serious adverse (flu) vaccine reaction that affects my nerves, (Brachial Neuritis) so all this is quite interesting.
How are you controlling blood counts now?
I've also seen IVIG discussed for nerve conditions, it counteracts IFN gamma, which is relevant to my condition and the vax that caused it as well as other nerve conditions. Has this treatment come up in your discussions?
This report is on the point, but probably not for your benign MS condition. But the mention of IFN-B is notable:
"Four double-blind trials in relapsing-remitting MS have demonstrated that IVIG reduces the relapse rate and the number of gadolinium enhancing lesions, and in this respect seems comparable to established therapies in relapsing-remitting MS, i.e. interferon-beta "
I emailed him when I found out I had MS. He then said INF a was contraindicated due to the autoimmune disease.
After I got out of the hospital after 3 days I saw my neurologist who diagnosed my MS as benign. Said I had it for years and never knew it and I have no deficits. He said most of the time this type doesn’t do much. And said it was up to me on whether I wanted to treat or not. He said if I was his daughter he wouldn’t and would wait. I did ask if I wanted to treat what he recommended which was beta INF.
Since all of this I have spent time looking at studies and articles. I have found a few from the 90’s they looked at alpha INF and potential improvement and if patients had worsening side effects for MS. They found that not only were the side effects not really different but MS improved. They used Roferon which I know is discontinued as of 2020 due to financial reasons and they were transitioning anyone on it to pegysays. Obviously in the 90’s and until 2021 Besremi was not around. And no reason for MS docs to revisit it because their are sooo many MS options.
At the time when I emailed him my counts were bad but stable so MD Anderson doc said let’s just watch and keep f/up. I had phlebotomy in October and I am on ASA. My Hct responds well. It is my PLTs and wbcs that are the problem. My wbcs started going up after my Covid booster after I had Covid 3mos prior. I also found ONE article noting the phenomenon of MPNs and MS. The person who had the closest course to me was on both INF alpha and beta. I am hoping I can present my case and take Besremi as it is in my fridge! I got approved right after all of this. But if not and he says HU then I plan to start INF beta to see what it does for both conditions. I will also be printing that article from today. I have at least 3-4 articles that will hopefully make him feel more comfortable. As well as approval from my neurologist. I just told myself in 2023 I will try at least one type of INF!😀 I will keep you posted. Pretty sure I am going to make an interesting case for him.
Will be interesting of you end up on beta, you'll probably know soon after whether it can help MPN by watching the PLT and wbcs.
Have you done a Jak2 allele measurement? Reductions there would be the final evidence the beta can work for you if you end up on it. I suspect there is zero public data on this result.
The hematologist. The neurologist will prescribe the INF b and will likely be monitored by hematologist. But my MD Anderson doctor and neurologist share an EMR. And I am lucky because I know my local hematologist so I can keep him in the loop through texting. My guess is they will work together but also stay in their lane. Since I am a PA it makes it a little easier since I am in the medical community already.
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