Factors Informing Selection and Use of JAK Inhibitors in Myelofibrosis

Transcript:

James K. McCloskey II, MD: So, thinking about these drugs that we use in less cytopenic patients. Geeny, could you talk to us maybe about the—I know we touched upon some of this, but, really, the safety profiles for ruxolitinib and fedratinib?

Geeny Lee, PharmD: Ruxolitinib and fedratinib do have some overlapping [adverse] effects, but they also do have some unique toxicities. So to go over each, some [adverse] effects of ruxolitinib include cytopenias. I think we mentioned it before about thrombocytopenia, anemia, and neutropenia. So, for these, really depending on the degree of cytopenias, we may have to reduce the dose or even hold the treatment. And ruxolitinib has also shown to increase risk of various infections. So we do want to monitor patients closely for any signs and symptoms of infections and treat promptly if they do develop any. And, lastly, again, Dr McCloskey alluded to this earlier, but if we do discontinue ruxolitinib abruptly, patients can develop a form of withdrawal syndrome or exacerbation of symptoms. So it’s really important to also counsel patients about not stopping treatment on their own. And if we are planning to discontinue treatment with ruxolitinib in a patient, like Dr McCloskey said, we do want to gradually taper them off rather than stopping abruptly.

And as for fedratinib, we can also see some cytopenias, especially anemia and thrombocytopenia. Again, depending on the degree of cytopenias, we may also have to interrupt and adjust the dose. And something that’s a little bit different with this medication is at the most common nonhematologic toxicity that we see with this medication is GI [gastrointestinal] toxicity that manifest as diarrhea and nausea and vomiting. So for nausea and vomiting, we can actually prevent with prophylactic antiemetic with something like 5-HT3 antagonist. And for diarrhea, it’s important to counsel patients to monitor closely. And we can also treat with anti-diarrheal medication like loperamide. But if we are seeing severe GI toxicity that does not respond to supportive care within 48 hours, we do have to hold treatment until resolution and reduce the dose. There’s also a risk of hepatotoxicity and amylase and lipase elevation. So we do want to monitor these labs at baseline and then periodically thereafter. And the last adverse event that I want to highlight, which also Dr McCloskey alluded to earlier, is encephalopathy, including Wernicke’s, which is a box warning for this medication. And in the clinical trials, this was a rare occurrence, but it can be severe. So, we want to obtain a thiamine level at baseline and monitor periodically throughout treatment. And if patient does have low thiamine level at baseline, we should definitely replete prior to starting them on fedratinib. So, with everything said, Danielle would you be able to highlight which patient population we may choose to use ruxolitinib versus pacritinib versus fedratinib?

Danielle E. Marcotulli, APN: I think when the patient comes in, every patient is so different. So if someone is coming into the office and their counts, they have these really robust counts, I think Jakafi would be a great drug for that person. You’re not worried so much about the cytopenias. I think Dr McCloskey had mentioned earlier, fedratinib. We don’t use it so much, but I think that it does have its place for more of the proliferative disease. And there is pacritinib too. So that’s classically, I think, even when we first started using it, it was that classic pacritinib patient with very low platelets, this is a great drug for them. I think even more so now, we’re using pacritinib in patients even with a very good platelet count whose primary problem is the anemia to spare them from some of the [adverse] effects from something [like] Jakafi. So, I think again, each patient is very unique, and I think these drugs each all have their spot in the different types of myelofibrosis patient.

James K. McCloskey II, MD: Right. I agree with that totally, Danielle. I think that…to highlight what Danielle is saying, pacritinib obviously was approved based on the data from these studies looking at thrombocytopenic patients and that, as people might be aware of, the FDA approved indication—I think Geeny mentioned this earlier—is for patients with platelets counts less than 50,000. Obviously, we understand that that FDA assigned that label based on the data that they’ve been provided. However, many of us, including the panel at the NCCN [National Comprehensive Cancer Network] recognized that…the data [were] primarily in these patients with … thrombocytopenia. But we still have these patients who have an unmet need that they’re not responding to ruxolitinib or…maybe they are so anemic, I can’t give those drugs. And so, the NCCN has added it now as a treatment option that’s endorsed by the expert panel there…, again, as frontline [treatment for patients] with platelets less than 50,000 but for any patient in the second line irrespective of platelet count. I think that that’s why…Danielle is mentioning we have many patients who are deriving benefits from this therapy despite not being profoundly thrombocytopenic.

Transcript is AI-generated and edited for clarity and readability.