Advances in the Treatment of Myelofibrosis - Episode 10

Second-Line Therapy for High-Risk Primary Myelofibrosis

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Second-line treatment considerations for a 75-year-old man with high-risk primary myelofibrosis who was previously treated with ruxolitinib.

John Mascarenhas, MD: I think to keep us on track or try to keep us on track, I'm going to move to patient case number 2, and this is a 75-year-old man who presents with shortness of breath, drenching night sweats, and fatigue. His past medical history is significant for a diagnosis of high-risk primary myelofibrosis for about a year. His baseline platelet account was 81,000 and started on ruxolitinib and is currently on 10 mg twice a day. Now his platelet counts dropped to 37,000 and his hemoglobin is 8.2 grams per deciliter. So the question to the audience is how would you treat this patient who has worsening thrombocytopenia on ruxolitinib? [A] transfusion support; [B] ruxolitinib at a higher dose; [C] pacritinib; [D] momelotinib; or [E] fedratinib.

Please submit your vote. Raajit, if you have a patient who's perhaps enjoying the benefits of ruxolitnib but is dropping his platelets to 37, 000, what is your treatment decision? Do you just treat through that with transfusions if needed? Do you jack up the dose of ruxolitnib? Do you move on to another JAK inhibitor? What would you do?

Raajit K. Rampal, MD, PhD: I would not increase the dose of ruxolitnib. I think that we can cross off the list but if someone's having a benefit, we have to be a little bit careful. Because, of course, going by the FDA [ US Food and Drug Administration] label, we need to attenuate if not stop ruxolitnib which, of course, we cannot do suddenly and risk withdrawal syndrome. In a practical sense, one could attenuate the dose of ruxolitinib and see if the platelets get better, do they improve, and then maybe re-challenge. That is not an unreasonable option but another clear option would be to consider switching to that agent to pacritinib, which will hopefully be approved soon. Again, in this particular scenario, we have a highly symptomatic patient. They need JAK inhibition and in this circumstance, pacritinib wouldn't require dose modification due to the thrombocytopenia and may be almost a perfect fit for this type of patient.

John Mascarenhas, MD: And Srdan? I think Raajit laid it out very nicely from an efficacy standpoint. From a safety standpoint, are there differences in toxicity profiles amongst these drugs?

Srdan Verstovsek, MD, PhD: There are some but they don't really affect the management too much and the 1 option here on the list I see, was fedratinib. Fedratinib has some mild GI [gastrointestinal] toxicity, nausea, vomiting, and diarrhea that you can treat easily with the prophylactic antenna and the area or antenna nausea medications. The same applies even less commonly with pacritinib. The advantage of these other agents, pacritinib in particular would possibly be considered as a first choice in patients that have platelets of 81,000 because the intensity matters. There is no need for those adjustments. The same applies to fedratinib if you want to discuss the other 1 too. This is the area where we expect new developments with the development of pacritinib and understanding what's the best approach in a frontline setting with having those 3 drugs in this gray area, in patients with low platelets. When the platelets go down to 37,000, certainly, this is not easy to manage with the currently available medications, so we welcome the new development of pacritinib.

Transcript edited for clarity.