ASH 2024 Highlights Podcast with Dr. Claire Harrison- HealthTree Foundation

[HungryB]

I wanted to share a podcast episode that Dr. Claire Harrison recorded with the HealthTree Foundation. This episode covered highlights from the American Society of Hematology (ASH) 2024 conference for MPN patients. Highlights for PV, ET, and MF were discussed during this episode.

healthtree.org/myelofibrosi...

[Tintins]

Thank you for sharing this link. A very informative podcast. So much work is being undertaken to treat MPN . Amazing.

[HungryB in reply to Tintins]

I'm glad you enjoyed it. The work being done is truly remarkable

[EPguy]

Some select notes:

--Higher BMI correlates to lower Jak2 allele (VAF), observed in humans. Obese mice with pre existing low Jak2 level "didn't develop the phenotype of PV, so high hemoglobin, or if they did, they developed it later and they lived longer."

"not just about the JAK-2, it's something else", this matches other recent threads, Jak2 by itself is looking less important than other factors (non-drivers ...?)

she relates inflammation to the obese observation. No follow up but usually obesity leads to higher imflam, suggesting an inflammation correlate is a good thing for Jak2 MPN. Hope she adds more here.

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--For MF the combo of IFN and Fadratinib (a Jak inhibitor) allows much lower dose of IFN and complimentary actions of each. She notes that Fadratinib is more a Jak2 inhibitor while Rux is both Jak1 and 2 (by design as I've posted, with the Jak1 part possibly being one reason for its immune suppression.)

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-CALR: " we found that Ruxolotinib and Interferon were able to reduce the amount of calreticulin." (calreticulin is the full name for CALR, I didn't know that). But Anagrelide for ET "was associated with significant increases in caloriculin and burden." "we've known for some time that anagrelide is associated with an increase in fibrosis". More indication that Ana has some negative sides.

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-CALR new treatments: "there are two or three caloriculin-targeted therapies that are being tested at present" Specifically progress for one using CAR-T, these have been discussed in prior posts. (In autoimmunes, CAR-T is being replaced with iNK, supposedly less toxic and easier to do, maybe MPNs will also benefit.)

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-HU benefit: In an ET study mostly using HU they found not surprisingly "for those patients who achieved this (blood count) control, they were less likely to get a blood clot, so thrombosis, arterial or venous" but also she said "and they were less likely to develop myelofibrosis".

Also in PV ". Regardless of the treatment, that if you achieved a complete hematological response, then patients had a better event-free survival, which was thrombosis, hemorrhage, transformation, death."

From this, getting CHR (compete blood response) improves long term outcomes, she did not mention mutation level here.

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-Claire Harrison (22:11) Likely benefits for early intervention, but which treatments are low risk enough for this use?

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-New PV treatment for HCT control- "Divesiran was well-tolerated without dose-limiting toxicities." This is after the same target, hepcidin, as Rusfertide, but seems to be a newer way to do it. Many members without HCT control on IFN could benefit among others.

I found the study:

ashpublications.org/blood/a...

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"Physicians, you need to take note more about your patient's symptoms. Patients, you need to make sure your physicians listen to you about symptoms. " So true for so many diseases.

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" P53 is really important...there was a lot of discussion about p53" it is a known negative prognostic. "And if p53 isn't working, then usually they (bad cells) don't die" Harrison said "A small amount of that mutation can sit there for years and years and years" so it's not necessarily always bad.

From later in the interview:

Navtomadlin may address p53: "So Navtomadlin reduces the effect of MDM, which releases P53 and then in theory, disease cells die". "...reduction in amount of mutations, reduction in fibrosis, and also reduction in CD34 positive cells, so that's leukemia cells or blast cells"

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Harrison's group produced an algorithm "that says, these patients can delay a transplant decision, and these patients need to go soon to transplant"

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New real world data showed for Momolotinib "it reduces symptoms, but it also improved anemia and made some patients no longer need to have transfusions. And it did it without any new side effects being reported"

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"fadratinib worked often at full dose for patients with platelets in what I would call the gray zone, 50 to 100...Below 50, we have to adjust the dose."

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Combo for MF or ET, not clear, of Imetelstat (telomerase inhibitor that prevents cancer cells from dividing) with Rux- "well tolerated and yes, spleen and symptoms, but also reduction in molecular burden and reduction in fibrosis."

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Several other combos discussed

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They encourage pts to join clinical trials.