Expert Insights into the Treatment of Myelofibrosis - Episode 6

Therapy Strategies for Primary Myelofibrosis

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Raajit Rampal, MD, PhD, shares the treatment options he would consider for the presented clinical scenario.

John Mascarenhas, MD: In this case, this treatment-naive patient with a very soft platelet count of 47,000 per mm3—close to 50,000 mm3—is clearly in need of symptom relief and perhaps could even be a transplant candidate down the line. Raajit, how would you treat this patient?

Raajit Rampal, MD, PhD: Against the backdrop of what we’ve already discussed, this is where pacritinib has been approved as a frontline indication for patients with a platelet count under 50,000 mm3. That would be the leading candidate. Are there alternatives? Why or why not would we choose those? Could one conceivably start low-dose ruxolitinib in this case and try to up-titrate the dose? That has been studied specifically in patients with platelet counts of 50,000 to 100,000 per mm3, where the dosing is 5 mg twice daily per the FDA label. There have been studies to try to increase that dosing to a dose intensity of 10 mg twice daily, which is successful in a proportion of patients.

As we’ve been saying, the problem here is, what are the expected adverse effects? We know that the inhibition of the JAK-STAT pathway will cause blood counts to go down with almost all JAK inhibitors, specifically platelets and red blood cells. In this particular case, we know from the PERSIST studies that a proportion of patients will have stabilization, if not some degree of increase, in their platelet counts with pacritinib. As Srdan pointed out, the same thing is true with the red blood cell count. Those are reasons to think about pacritinib in this situation.

The second issue has to do with dose intensity. Per the FDA label, we can use the full dose of pacritinib in a patient like this with a platelet count of 47,000 per mm3. Why is that important? If we think about ruxolitinib as an alternative in this situation at a low dose, it’s clear from retrospective analyses of the COMFORT data that dose intensity matters. If you look at the degree of spleen shrinkage in a patient, it’s proportional to the dose of ruxolitinib, with higher doses showing the maximal benefit, particularly once you get over 10 mg twice daily, whereas with 5 mg twice daily, there’s minimal benefit to spleen volume reduction.

The same is true of symptom response. Interestingly, the data with ruxolitinib show that there seems to be some correlation with survival in the degree of spleen volume reduction, likely as a biomarker of disease responsiveness. Either way, in this situation it would be suboptimal to use a dose of ruxolitinib 5 mg twice daily when you could alternatively use the full dose of pacritinib.

Transcript edited for clarity.