A panel of experts share how they select between treatment options for patients with MF.
Ruben Mesa, MD: Let’s delve a little into how we might use some of the agents, perhaps stratified a bit by when they might be approved. But Angela, Stephen had shared with us that pacritinib is helpful for people with thrombocytopenia. If that drug is approved sometime soon, where might you think of that, in the front line, in the second line, certain platelet levels that might engage you to consider that drug?
Angela Fleischman, MD, PhD: That’s a great question. It really will be great to have more JAK inhibitors in our tool set because as each patient with myelofibrosis is unique, there’s not a one-size-fits all JAK inhibitor. I think based on the anticipated approval, for somebody with a very low platelet count below 50,000 pacritinib may be a very clear choice there. However, for people whose platelet counts may be above 50,000 and may technically meet appropriate criteria for ruxolitinib or fedratinib, but who are the cytopenic type of person, where you’d be concerned about giving another JAK inhibitor that might bring them from anemic to now transfusion-dependent, or are concerned that you don’t have much cushion with their platelet count, pacritinib might be an appropriate go-to option for these more cytopenic patients with myelofibrosis [MF]. Whereas if somebody is very proliferative and you’d like to cytoreduce them, then maybe one of the other JAK inhibitors might be a clearer choice than pacritinib.
Ruben Mesa, MD: It’s interesting. I think we’ll learn a lot more as we have a therapy in the clinic, and we have more flexibility. I was talking with some of our colleagues who do stem cell transplantation, and they state that it is their goal to sometimes have the patient have the best JAK inhibitor response pretransplant, shrink the spleen to the maximum degree. And sometimes as patients are progressing to transplant, they’re pretty cytopenic, some of them are on fairly modest doses of [ruxolitinib]. And they’re pretty excited about trying to jump in with pacritinib and see as a run into transplant, might that be one important niche?
Angela Fleischman, MD, PhD: Correct, yes.
Ruben Mesa, MD: Stephen, any thoughts? Where might it fit for you, in maybe that 50,000 to 100,000 [platelet count] range? I think Angela raised an important point. Technically on-label, all 3 JAK inhibitors would have that 50,000 to 100,000 range, and there would be some individualizing features. What might you consider as you try to think whether this is someone I’m going to start with pacritinib, or fedratinib has some data in that group? How might you sequence it?
Stephen Oh, MD, PhD: I have a similar view. For sure below 50,000, I think that if it’s available, whether it’s up front or subsequent to a trial of another JAK inhibitor, I think pacritinib is the obvious choice there. In that 50,000 to 100,000 range, I agree that there you could be considering, for instance, ruxolitinib or pacritinib. And keeping in mind that while ruxolitinib could be used, it is often very difficult to get up to a dose of ruxolitinib to achieve a meaningful symptom and spleen benefit. If I can’t get above 5 mg twice a day with ruxolitinib in that kind of category, I’m not typically expecting to see a robust improvement in spleen or symptoms. We know from the literature that, in general, you need to get to 10 mg BID [twice a day] of ruxolitinib to see a substantial improvement. So there I think it’s potentially reasonable to consider pacritinib, and maybe that would also be reinforced by that particular profile of that cytopenic patient with MF. That’s in particular where there are going to be a couple of choices, but again, reasons why upfront pacritinib in that setting could be a good choice. And even if one might consider using ruxolitinib initially, it might be apparent right away, let’s say the platelet count starts dropping, and again an inability to get to that 10 mg BID dose of ruxolitinib, then it might be a relatively early switch to pacritinib.
This transcript has been edited for clarity.