Dr Mesa on MF prognostics, Rux and SCT

[EPguy]

Some detailed info in Dr Mesa's thoughts in a 2020 interview I came across:

-For some MF patients Rux is working well and long term: <<There are patients from the phase 1 study of ruxolitinib (this dates to early as 2007) at our centers that are still on the therapy. These are individuals that had expected survival [times] of under 3 years.>>

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-HU is good for ET, ok for PV (but INF may be better), and not great for MF (but was only option before Rux) . <<In myelofibrosis, it might help with leukocytosis but doesn’t do much for splenomegaly symptoms, anemia, fibrosis, or progression toward acute leukemia>>

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Rux dosing is often too low and 2x 15-20 mg/day is desirable. (This seems less an issue with INF where the "right" dose is all over the place) <<There are likely too many patients out there on a suboptimal dose of ruxolitinib...rapidly increasing the dose where you truly see a significant reduction in the size of the spleen and improvement in the symptoms [is necessary]. If you’re not achieving that, then that is when it’s important to think about second-line therapy, dose adjustments, or a clinical trial>>

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-Possibly actionable info: Dr Mesa says SCT is most successful when done before you really need it, before Rux may start to fade <<the best time to have a transplant is probably before either the patient or physician really feels the patient needs one. It’s during their optimal JAK inhibitor response that they probably do the best>>

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-If clinical data are higher, and MF patient has any of these mutations- ASXL1, EZH1/2, IDH1- there is increased advantage to consider SCT. <<The absence of a bunch of these somatic mutations is somewhat reassuring.>>

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-Dr Mesa says mechanical spleen size is not itself important but <<the spleen is a good barometer of the quality of JAK inhibitor response, and responding to JAK inhibitors improves survival>>

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-<<On Rux anemia is the most functional difficulty>> while PLT level may be low but is less a driver of discontinuation. (See Vonjo Jak-i for low PLT problems) I've posted on the anemia issue. The new Momelotinib should help here. From an old post: "I just saw in the business news that Glaxo Co is buying an MF drug maker, Sierra Oncology, for its new drug Momelotinib. Implication is Glaxo expects FDA approval. Momelotinib failed its first round trials against Rux, but in the context of anemia it's looking good enough for Glaxo to spend $1.9 billion on it."

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-On another approved Jak-i, fedratinib, Dr Mesa seems not too impressed vs Rux. <<it’s not clear that there is necessarily a clear advantage between one or the other>>

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targetedonc.com/view/mesa-d...

[Ettiel]

Hi ETGuy - Thanks for this very interesting interview with Dr Ruben Mesa on MF Prognostics and Ruxolitinib. I’ve been on Ruxo for MF nearly three years now and hoping to be one of those for whom it continues to work for a lot longer! It has worked wonders for me so far so fingers crossed! I hope your post-Covid symptoms have eased by now and that you are in top form.

Ettiel

[Dan39]

Thank you for your helpful and informative inside! GBU

[amalekh]

Very promising conclusion!

Thanks for posting.

Malek.

[Meatloaf9]

Thank you for posting this article. I do wish he would have made a comment on age limitations. If it was in there I missed it. I will soon be 73, my MPN specialist said that 73 was typically his limit for referring patients for SCT. He did say he might consider it up to about 76 for healthy patients. What is a healthy MF patient? What I am wondering is if I should have another BMB and if I have early fibrosis should I then consider a SCT? My specialist did not recommend another BMB. My timeline seems to be running out. I hate the thought of surrendering to these diseases. What do you think?? My current Dx is PV, my one BMB was 4 yrs ago.

[Otterfield in reply to Meatloaf9]

A healthy MF patient is, as I understand it, one who is relatively fit and doesn't have any co-morbidities. I am considered healthy, even though my fibrosis is Grade 3. If you had only mild fibrosis, I don't think an SCT would be advised as you would be relatively low risk.

[Meatloaf9 in reply to Otterfield]

Hi, I hope things are going well for you and the SCT will soon be over and you are cured. I think Dr Mesa said in this article that the best time for a SCT may be when the patient and Dr both feel that you may not need one, before you become high risk. I realize that a SCT is not something to take lightly, but once you have MF it is the only possible curative option, is it not? I think the only other option is to take medications and when they quit working, well....... I may already be past the age limit for many centers that perform SCT. Were you told of any age limits?? Thanks for your reply, we are all praying for you. Best.

[Otterfield in reply to Meatloaf9]

Thank you for your good wishes - I'm still waiting for a new admission date after my donor caught Covid. It's true that an SCT is the only (potentially) curative treatment and deciding when to have it is inevitably a gamble. I chose to go ahead as I knew that Ruxolitinib, which was a miracle drug for me, would stop working. And when it did, I may have developed another health issue, making a transplant much more risky. It's risky enough, something I try not to think about.

I'm 60 and nobody has ever mentioned my age as a factor.

[EPguy in reply to Otterfield]

It seems you're consistent with Dr Mesa's idea here, SCT while response to treatment is still good. I think age 60 is well in the SCT range, so they didn't have concern. Look fwd to hear your progress.

Covid is everywhere lately, the ba.5 Omicron is not nice.

[EPguy in reply to Meatloaf9]

There is an age reference <<if one is 45 years old and healthy and the other is 70 years old with comorbidities, there’s no way those patients are doing the same>>

It's in the context of risk, I think he means bad mutations in the younger patient are not by themselves causing highest risks. But a combo of higher risks point to SCT. My take is the higher risk pts should not wait for things to get worse.

Dr Mesa discussed SCT in context of MF. I don't think a PV patient is likely to get approved for SCT, it is interesting your Dr is discussing SCT with your PV Dx. Has Dr noted specific risks you have that merit SCT discussion? What did your BMB report? Are your CBCs changing recently?

[Meatloaf9 in reply to EPguy]

My specialist only discussed SCT because I brought it up and was asking him questions about it. He said he doesn't refer patients for SCT after age 73 that puts me squarely on the dead line in a couple of months. I was wondering what if I am diagnosed with MF at 73.5 or 74 so I asked about it. I have the dnmt3a mutation and immature granulocytes in peripheral blood both of which some specialists believe promote progression, my guy says the jury is still out on both those two issues. My AB went from 27 to 50% in 3 years, that sounds pretty rapid to me . He told me that about 20% of his PV patients eventually develop MF. Sounds like a lot to me. He does not do SCT for PV. My H & H were ok this past week. Thanks for sharing this article. Best to you.

[EPguy in reply to Meatloaf9]

I recently posted on hi risk mutations vs MF. According to that, dnmt3a is not in that category in this presentation.

healthunlocked.com/mpnvoice...

Any progress with your insurance co on the Besremi co pay?

[Cja1956]

This is a very interesting article. I’m post Et Mf intermediate 1. I know I’m not ready to have a SCT yet. I’ve been evaluated a couple of times. Im only on HU and baby aspirin only but I’ve been on Ruxo in the past which eventually failed me. I’ve also been on Fedratinib but it made me super tired. One of my doctor’s that I saw for a second opinion told me that having a SCT will not make a difference in my life expectancy. So I probably won’t have one.

[EPguy in reply to Cja1956]

Was that 2nd opinion because Dr feels you're low risk MF?

[Cja1956]

My hematologist suggested I see this doctor because I was questioning whether I should get a SCT. Both doctors agreed that I wasn’t ready. They want you to be at intermediate two when you have the transplant. The second doctor did say that I had a median life expectancy of 9 years from 2019 from when I was diagnosed at age 63, so that was a little disconcerting. It’s all very stressful because I’m 66 now and the doctor that does the transplants only does them until age 70 here in Florida.

[Timjonze]

Great summary thanks for posting