In this thread I made summaries of some of the videos that Hunter kindly provided.
A top stand out item seems worth its own discussion. Raajit Rampal showed prior and current ET risk rating factors, see image. Here is my note:
"New ET thrombosis risk ratings: PLT counts are no longer in there. Used to be >150000, now not even listed. Jak2 status is now important."
The general idea is more focus on genetics.
There are very many posts on the Voice with concerns about PLT, does this mean we don't need to worry about it? (at least for ET)
Hunter added more context that was not in the posted videos, see here:
"As I recall Dr. Mesa also addressed this during the Q&A session. There is thinking that the value in cytoreduction for thrombocytosis is not in the absolute number, but in the delta (overall change in value). One of the docs also noted that the cytoreduction platelet target may need to be different for different patients. Some need a lower level than others based on actual symptoms that occur. "
My assessment is that answer is more nuanced than than PLT numbers alone. Part of the issue is that so many focus on the risk of thrombosis, when there is also risk of hemorrhage and microvascular events. We have seen repeatedly that the absolute number of platelets does not correlate with degree of risk from thrombosis. There is not 2x the risk at 800 compared to 400. It just does not work that way.
It is true that at 800 there is an increased risk of hemorrhage compared to 400. The bottom line is that the higher platelet levels go, the higher the risk of hemorrhage. This is more than developing Acquired van Willebrand Disease. There can be more subtle levels of hemorrhage too. Regarding AcqvWBD, there is evidence that it can occur at levels much lower than previously thought, perhaps as low as 800.
Then there is the risk of microvascular events, where blood cells interact with the vascular endothelium in a different way. The "extra-sticky" phenomenon. There can be a variety of different types of microvascular symptoms. These are not the same thing as thrombosis.
These three issues are still only part of the MPN puzzle. There is also the overproduction of inflammatory cytokines and all the issues that the pro-inflammatory environment creates. There are all of the secondary symptoms we experience like fatigue, insomnia, pruritis, and all the rest.
The move away from focussing only on an absolute number of platelets is an important step forward in treating MPNs where thrombocytosis is evident. What matters is controlling actual symptoms and managing the impact of the MPN on the individual patient based on how that person presents. The answer can be different for each person. Some people do need to keep platelets below a set level. Others do not. Some find they feel better when platelets are below a certain level. Other do not. (I suspect this has more to do with controlling cytokine levels than platelets. The two things just correlate).
It is very hopeful that we are moving into a more nuanced and individualized approach to MPN care. We will all benefit from this. It does require that we engage providers with the expertise to provide individualized MPN care. It is on us to ensure we receive this type of care.
One take away is many members are extra worried about PLTs ~400-500, and this here is some evidence that as you say, this number needs lots of context.
Personally, I am always skeptical when I see these risk profiles. Why? Because to me, the bigger threat of this disease is progression to MF/AML, not thrombosis. These risk criteria are misleading in that they are based purely on risk of thrombosis, NOT disease progression. Being in the “very low risk” group does not mean your overall risk is “very low” - it means your risk of thrombosis is low. Your risk of disease progression is just as high as anyone in the other categories.
You've nailed it, most us victims are really focused on progression while the profession looks at specific adverse events. That was all they could do till recently so it's reasonable, and probably rational. But we are not required to be perfectly rational in all matters.
Anyway there is lots more focus on progression risk lately, esp using the new genetics that are the subject of the videos Hunter posted. What we will need next is actions we can take to cut prog risk. Right now INF has that potential and is getting its day in the sun. We otherwise await all the new targeted therapies.
I did hear some comments in past MPN conferences that some docs were surprised that patients were so concerned about progression. They did not realize that patients valued reducing risk of progression that much. I suspect this is, at least in part, because until recently there was nothing doctors could do about the risk of progression. So they just ignored it and focussed on what they could control.
I think we see the same thing with quality of life symptoms. Some doctors do not understand how a MPNs affects patients nor do they know what to do about it. Sadly, some even blow off MPN patient concerns, discounting what they do not understand.
The good news is that in the MPN Specialist community there are docs who do understand. They also have an emerging array of treatment tools they can employ to help patients meet their goals. It is up to the patient, however, to enforce prioritizing their individual goals. We have to tell the doctor what our goals are, what our risk tolerance is, and what our treatment preferences are.
Agree about only recently having options to act on progression, as in other posts too. I think INF for now is the only approved therapy that holds this promise. Maybe Rux?
My Dr does care about progression and QoL. He helpfully reminded me at our 1st meeting that my condition is serious.
He specifically recommends Rux for symptom relief; he says most his pts on it get quick relief. I'm up for toughing out INF to seek its best potential. I would consider a low dose Rux combo to help along but absent large trials there my Dr does not want to try that.
Glad to hear your doc is in sync with your treatment priorities. I am likewise blessed with docs who have the same priorities and who listen to what i care about. I might at some point opt for a combination of Besremi and Rusfertide when it becomes available, More opportunity to be on the cutting edge! I do se real potential in combination therapies tailored to the needs of each individual patient. Hopefully we will reach the point where docs will be able to tailor the treatment based on the genomic profile of each individual. The future for MPNs could get quite interesting.
I am thinking just an occasional dose. Similar to how we would use a phlebotomy. I have heard some rumbling that Rusfertide may come out with an autoinjector. That could make dose titration an issue.
Another big item missing is Quality of Life. Many of us (count me in ) care lots. We can hope some of this genetic stuff will help figure it out. On a bad day I'm more focused on the Q than the L.
Agree 100%. The MPN profession behaves as though it fears interferon drugs because they usually slow or stop progression to advanced MF/AML hence represent a potential threat to their future income goals. After all, the big money in the MPN disease profession is made from treating advanced disease patients; i.e. via their frequent office visits, biopsies, clinical trials, blood transfusions and stem cell transplants.
That’s quite a US-centric view (which I understand). In the U.K. the position is somewhat different. There are are huge financial constraints and resource issues within the NHS. I doubt wracking up repeat hospital visits, interventions and encouraging disease progression is anywhere on the agenda. Quite the opposite. And I really doubt any physician of even limited reputation would be aiming to balance their books by encouraging by neglect, their patients ill health.
Aside from that many (all?) of the world leading MPN specialists in the U.K. don’t have private practices. Aside from ethical positions, it’s a niche market. And even if you have extremely good private medical cover as a back stop to NHS care, it’s unlikely to cover chronic conditions.
What I do think is true, financial considerations aside, doctors can operate on the ‘if it ain’t broke, don’t fix it’ principle and are more likely to offer / continue drug interventions that they know are effective and more importantly, well tolerated. The fact that they are relatively cheap and easily available is also a factor.
And there are certainly factions of enthusiasts for certain types of interventions - particularly in earlier or experimental stages. Money will certainly be a consideration - but not in the way you suggest. Awareness, knowledge and the economic constraints of access to treatments are, I suspect, much bigger drivers.
Back in 2011 the compassionate Danish researchers were already addressing the progression threat issue by promoting early intervention with pegylated interferons. In 2011 Danish researcher Dr. Hans Carl Hasselbalch wrote this:
"It is argued that in 2011, the bulk of evidence for the efficacy and safety of pegylated interferons in treating patients with these neoplasms favors the upfront use of pegylated interferons, the goal being to influence the development of the disease at the molecular level and revert patients to a stage of minimal residual disease/operational cure instead of progressive clonal evolution, genomic instability and leukemic or myelofibrotic transformation during long-term treatment with hydroxyurea."
Thankyou for the chart re: risk level. Is there any information that quantifies what is meant by ' high risk'? Eg- 20% chance of a stroke or some other % risk?Thanks
Unfortunately I've never seen seen a risk category specified as a probability (%). I think it's because the highest and lowest %'s are so far apart that it doesn't add much info.
We do see averages and medians in plots, such as event free survival for example. These do have meaning when different groups are properly compared ie with/without therapy "X". But for one of us alone, these averages don't add much predictive info.
In simple terms, there's just too much uncertainty. A good example is the subject here, being constant changes to what is even defines a risk level.
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