HU resistance and bad outcomes

[EPguy]

We've discussed in some posts comments from Drs. Harrison and Gotlib on the high risk for pts intolerant/resistant to HU. 5-7 X higher risk of transformation or death.

I found the source for this. It's a relatively old 2012 report.

The plot here is Risk of Death (A) and transformation to MF, AML (B).

"Resistance and intolerance to HU was registered in 11% and 13% of patients, respectively. Resistance to HU was associated with higher risk of death (HR, 5.6...) and transformation (HR, 6.8;...)" HR is the X increase in odds of the bad event.

"Median survival after developing resistance to HU was 1.2 years"

Important exception these days: Rux and IFN are available as alternatives so one can switch as soon as HU intolerance/resistance shows up.

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ashpublications.org/blood/a...

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As a side note, most or all studies for Rux enrolled the 24% of pts in this risk category. The generally positive results for this risk group are a pleasant outcome.

In contrast any prior HU users in the Ropeg IFN study were required to be HU tolerant. If this is true, the Rux studies vs IFN might been handicapped by this potential risk difference, although there is still no direct IFN-Rux study.

There is one new study ongoing, RuxoBEAT, where pts are not selected for HU intolerance. It's at only 6 months, but might be the best source for indirectly comparing Rux to IFN for PV.

[Aldebaran25]

The way I see it, at this point in MPN medical research, as patients we embark on a drug migration journey where each drug we try buys us time . Of course there is the individual element of intolerance (as you well know! ) but I consider that being on any one of these products will last only a finite time before dosage may need increasing and side effects get worse. How much evidence is available on long-term use of ruxolitnib?

By the way, you are brilliant at organising and comparing the results from research, thank you for doing this!

[EPguy in reply to Aldebaran25]

From what I'm finding lately Rux is getting the most rigorous and longest term prospective studies. 12 years for example. IFN has a great retro study we've discussed, but none that include the pre-planned end point of VAF reduction vs events, in contrast to Rux.

The complication with Rux has been handicapped in concept by its 1st trials being in the more challenging MF area, and its PV trials being with HU intolerant. We may see Rux in its best light with the ongoing RuxoBeat trial.

[mother2britton]

Thank you for posting.