This is a recent presentation br Dr. Hans Hasselbalch regarding the role of inflammation in MPNs and the implications for treatment. It covers quite a lot, including CHIP, MPN comorbidities and possibilities of combination therapies.
Dr. Hasselbalch is a strong promoter of the use of interferons in MPN treatment and in the importance of early intervention in MPNs. Not everyone is going to agree with his views. The presentation is intriguing and thought provoking even for those who may not fully agree with everything he has to say.
What a character that Dr H is! I actually liked that he talked very fast but leaves us those elaborate charts to look at later. That way I could get in his ideas before my dog walk this morning! Hopefully the frost is melted by now!
Thanks for this post! I have read MPN’s are a disease of inflammation. The video helps put it together and has a nice list of articles to go and reference. wishing you and your family good health!
Some charts early on noting TET2 seeming in an undesirable context but no follow up.
MPNs are about inflammation. What isn't? This applies to a great many other conditions and life in general.
Atherosclerosis is a large risk with Jak2+ mutation. ( I had zero plaque on a cardio test a couple years ago, maybe my lower allele is related)
11.3% of ischemic stroke pts are Jak2+, the regular population in a quick search shows 0.1 to 3%.
Stroke pts have HR of 2.4 for Jak2. I think he suggests all ischemic stroke pts get Jak2 test.
Abdominal aneurysm 7.2% are Jak2+. I have familial risk for that.
MP pts should check for osteoporosis.
"Only IFN -a2 can deplete the clone" We now know this is false.
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"IFN is safe". We see here that's true for most but a signif cohort of us is forced off for adverse events. In the Daliah trial he cited:
"The most common cause of treatment discontinuation was adverse events (HU: 6/38 (16%); IFNα: 71/165 (43%))"
And the Sjogren's risk found in the Bes trial is really happening here, among other less common severe outcomes. Our other meds don't regularly show these extreme outcomes. He should address this for completeness perhaps by discussing optimizing the dose.
He might say "IFN is great medicine for those who tolerate it".
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IFN leads to MRD (minimal disease) This has been ~20%, hence ~80% don't get there. But his idea of early Tx might nicely up that 20%.
His Ropeg chart is still missing the 5+ years result, as I've posted, post-5 year is missing for a reason.
Rux is called anti-inflam but not credited for clone reduction. This is a huge oversight. We know now Rux alone can and does target the clone. He should know better.
Statins can target the clone and enhance IFN benefit. He makes a strong case for taking stains for any MPN pt. I would like to start that, and Rux may be offering an excuse to do so.
Ditto re. no plaques with a relatively low Jak2 allele burden (20%). I nonetheless had a (tiny) ischemic stroke which ultimately led to Jak2 testing and the PV diagnosis. My hct, platelets, RBC are only moderately high so I assume it was behaviour of blood (or vein/artery wall) cells that caused the infarct in my case.
Hunter below also had no cardio plaques. So our tiny sample doesn't fit this part. Your point is good that other areas of the blood system can still make trouble.
I'd also guess that keeping blood counts good reduces this cardio risk.
His point about statins was the most interesting piece of information. That was the first time I had seen statins mentioned as potentially helpful. I need to listen to a few sections a second time, lots of good data.
I've been reading on that for a while. Maybe Dr Hasselbalch is the key source for this idea. As Hunter notes, statins are not entirely risk free, but maybe if one needs them anyway there is this extra benefit.
I think you make some very important points here which raise questions. I havnt watched the vid but don’t doubt your analysis. I’ve heard his talks at many conferences.
I note you write discontinuation from Inf according to Dr Hasselbach was 43%. Yes thats 43% (not 10-20%), Dr Hasselbach said to me in a consultation in 40-50% , that was in 2013, more recently I have heard him and the Austrian expert and Clair Harrison saying 50-60%. I hope all the Inf enthusiast posters on here take note of that. It’s still a very good drug but we have to be honest and realistic.
Re statins, I hear his arguments and I don’t know if he is right or wrong, all I can say is at time of writing I havnt heard any other expert recommending them and the experts I have asked specifically said they wouldn’t suggest them for MPN only. That may change as time goes on but it hasn’t yet. One also has to be aware of the other risks/benefits of statins outwith MPN.
I will also add that at the doc to doc conferences he doesn’t seem to get much agreement from the other docs there when he does a presentation, having said that he is one of the nicest docs you can meet,
The Daliah trial was known for a high drop out rate, a bit surprising he used it as a reference. You say more recently it was stated as 50-60%. That could be of particular import since dosing is a lot more informed post-2013. If he agrees with that extreme rate in more recent usage, it's most improper or even unprofessional that he not add that to any presentation on IFN.
I understand the 50-60% is pts that were forced off therapy vs just adverse events. In our very limited sample on the forum, my feeling is a large majority have negative sides, but a (still significant) minority are forced off IFN from them. If it's really 50+% then IFN is a "fair weather friend".
IFN history has it being an interim solution, for Hep C it is now largely obsolete. My neuro just told me that IFN-beta for MS is also "archaic". Lets hope for MPNs we get a similar future modern option with shorter fangs.
Thanks for your usual thorough and insightful review. While I posted this because it was interesting and contained some very useful information, I also did not necessarily agree with everything stated. We have to listen with open minds and skeptical ears when reviewing the information we are given.
On the affirmative side - I found the discussion of comorbidities related to inflammation very interesting and consistent with my own experience with inflammatory conditions. The comparison to Diabetes were very interesting as well. I particularly liked the way he structured treatment goals: Prevent thrombosis/hemorrhage, prevent progression into MF/AML, and Improved Quality of Life. Too many only focus on that first goal. Consideration of combination therapies is also worth moving forward.
On the skeptical side - I think the risks of interferons are understated. While I favor the use on IFNs as a first-line option over HU, I would never contend that it is without risks. Likewise the risks of statins. While it might have some benefit for some with MPNs, I question whether the risks would be worth the putative benefits for many with MPNs. I have a cardiac calcium score of 0. While that is only one type of arteriosclerosis, I would need a lot of convincing to consider a statin.
I definitely agree with your reframe "IFN is great medicine for those who tolerate it." That is the best way to state it. It can result in minimal residual disease. I suspect that starting earlier would be better for many people for preventing diseases progression; however, early intervention is not best for all.
As always, thank you for your insights and information. Wishing you success on your journey.
Good point on the diabetes comparison. My selected notes should have selected that. I don't recall any actionable effect of the similarity but if there is that would be neat.
My impression of statins is a fairly mild profile. But as you say, taking them just for MPNs should have deeper data to support it. I may have an excuse if Rux puts my cholesterol high. My husband cut his in half on a low dose, his cardiologist was impressed.
My rediscovery of that high rate of Sjo in the Bes trial was a wake up. Pts need to really pay attention to what's up.
On early IFN, getting to near zero VAF would be great, but as you say, there is a very non-zero risk during IFN therapy.
Re Rux and cholesterol, my total cholesterol was high recently, I saw my cardiologist who said because my HDL was so high it didn’t matter, I then had a neck carotid scan to check veins, all 100% clear, in fact when my cardiologist viewed the images of the scan his words were that the veins were pristine, zero build up. He reckoned my HDL was high due to lots of exercise. Tryglicerides were also below range, I eat health.
There is much debate about cholesterol, Dr Mercola has written interesting views on it and there is a book by UK doc Malcolm Mckendrick called “the cholesterol con”. The statin industry maybe driven by £$$ as opposed to the health of patients.
I am a firm believer of the role of inflammation in the development of many diseases. Before I was diagnosed with PV(2018) I consistently had a very elevated CRP number, for at least 15 years. My primary contributed it to my osteoarthritis and not cardiovasculer disease. She simply said I had a high imflammatory "state" in my body. Then came diverticulosis 10 years before PV. Dr. Hasselbach makes a very good point about the "gut". My past development of Atrial Fibrillation is electrical in nature, but who is to say that inflammation did not play a role in it too. I am happy to say that I currently take Besremi and Jakafi, so I hope I see a future where my allele burden(94%) will decrease. That was the percentage in 2018 and will find out soon of any decrease. Thank you for that video. It was very informative.
Amazing doctor and very informative video . I always suspected that inflammatory diseases are the cause of this Jak2 mutation but doctors said no it’s something else.
Thank you so much for looking out for all of us and posting all the information. Very helpful and gives us more hope that maybe one day this disease will be eradicated.
Great info thanks Hunter. Makes me want to start taking the statin my primary care doctor recommended for my elevated LDL even though my overall cholesterol is good. My concern about statins has been whether it will worsen my neuropathy. Would be great to have it help my ET.
Otherwise Dr. Hasselbalchs work here seems to be good for Jak2 MPN which is more likely to cause thrombosis. CALR folks don’t seem to have the same risk and don’t respond to Peg as well. My Allele burden rose during my 4 years of Peg. Also thinking more highly of aspirin use which I’ve increased to 325mg daily to keep some check on inflammation.
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