Rux and IFN combo therapy

[EPguy]

This recent report points to benefits of combining Rux and IFN. Of particular interest is the low doses that were enabled toward the end.

-Notable: "The JAK2V617F allele burden was significantly reduced 3 months after the start of treatment, and continued to decline from a median of 47% to 6%."

In the plot here from this report I've added the Ropeg (Besremi) results. Not necessarily comparable across different studies, including this one used PEG, but interesting. Even assuming the median start at 47%, combo got to 6% while Ropeg alone is 14% at 2 years. Shifting the combo to the lower baseline used in Ropeg, the end result is 2%. From the slopes it looks that the combo works faster than IFN alone. Hoping this study goes for longer for better comparisons.

Further, at just 24 months, 4pts (17%) were at <1% allele. Ropeg had 19% there at 5 years.

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In this recent thread, getting allele reduced is looking ever more important.

healthunlocked.com/mpnvoice...

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Low doses: at follow up, doses were just 45mcg/2weeks PEG and 5 BID(twice a day) for Rux. Rux pills go from 5-25, 5 being lowest possible dose. This contrasts vs Ropeg trial which used near the highest published doses for the study.

The main adverse event was anemia "Grade 1-2 anemia was frequent and managed with dose reductions." We're all for dose reductions. Seems high grade events were reduced but not clearly presented.

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I've posted before that IFN seems to lose some allele benefit after 5 years, on average, including hidden data from the Ropeg trial. Maybe this approach could help?

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Bottom line, powerful allele reductions at low doses in this small combo study.

This study is ongoing and they promise more/other data soon. For those doing well on either this may not be relevant. But for the many with adverse events on either, so far: "Combination therapy with the two agents may be more efficacious than monotherapy." Mr Dr is agreeable to this concept. But insurance coverage could be a problem.

ashpublications.org/blood/a...

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[Nikon7]

thanks for this post! Is there a process commencing for FDA or British equivalent approval, that you know of, of this combination treatment?

[EPguy in reply to Nikon7]

I'm not aware of any submission at all. It may be too fresh and new to get that started. But it's looking to me like a candidate for 1st line, or at least for all who do not tolerate or respond to IFN alone. Approval would help insurance quite a bit but the mfrs will need to cooperate otherwise it's $400k per year at retail prices and dosing methods.

[william-Indo]

I am at this combo treatment for a year now.The result is very good

[EPguy in reply to william-Indo]

I remember your using this, possibly the only member who has posted on it. What is your current dose? Bloods all in range, feeling ok?

Is there any trouble with the cost? It adds PEG+Rux could be expensive. My Dr says insurance (private in US) likely would not pay.

[william-Indo in reply to EPguy]

My current dose ispegasys 135mcg weekly

Jakafi 10mg twice per day

When used Jakafi alone, my HMC 48 (support with phlebotomy every 2 mo) and PLT more than 1 million.

All CBC in normal range now.

I do my treatment in Malaysia and the cost around USD.3K monthly, all cover by insurance (private)

[william-Indo]

Correction.MCH Should be HCT

[EPguy]

In the US the cost would be over ~30,000 per month, so it is a problem with current pricing.

While Rux-only didn't work, did you try IFN alone? Sorry if you posted already. Adding Rux is supposed to help with IFN tolerance among other benefits.

[Yanico]

Thank you for that. My allele burden only reduced to 89% from 93% on Pegasys. i haven’t heard of anyone with a burden that high. Obviously worried. Went from ET/PV to Myelofibrosis in two years. Was probably a year before that realistically as counts were high but GP didn’t spot it.

[EPguy in reply to Yanico]

There are members who have posted with VAF in 80's and 90's. At least one is stable with and feeling ok with PV I recall.

It is possible you could get better reductions with the IFN/Rux combo but there isn't a lot of data to know. But the lower doses they used here are appealing in any case.

If your MPN Dr is suggesting it and you can get it covered it seems a good option to try. Esp with lower dosing of Rux here vs Rux alone the anemia risk for MF could be less.

I would like to add a tiny dose of IFN to my Rux but for me it's likely too risky.

[Yanico in reply to EPguy]

Such a frustrating system in UK. Can get rux for P V in Scotland but not in England except for trials . Rux is approved for Myelofibrosis in whole of UK. Besremi not approved in UK as far as I know. Seeing MPN doctor on Friday so I’ll see what she is thinking now.

[EPguy in reply to Yanico]

I know there are many UK members on PEG, it's off label for any MPN but cheaper than Bes so can be easier to get.