Myelofibrosis Management: Current Treatment Guidelines

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Expert panelists share brief insight on the current NCCN guidelines for selecting treatment in patients with myelofibrosis.

Transcript:

John O. Mascarenhas, MD: All 3 of you are involved in the NCCN [National Comprehensive Cancer Network] Guidelines. I’m the only 1 who’s not involved. They get updated frequently, and MPNs [myeloproliferative neoplasms] have been included for some time, and there have been recent updates. Maybe you could share with the audience some relevant MF [myelofibrosis] NCCN updates that they should be aware of.

Andrew T. Kuykendall, MD: The NCCN Guidelines haven’t had substantial updates. There’s been tweaking of some things as we get new approvals and highlight different areas. But in myelofibrosis, we’re still stratifying patients: higher vs lower risk. [For patients who are] lower risk with symptoms, we’re treating them as high-risk patients. It’s important to note that these risk scores identify patients who should be considered for transplant. That’s the purpose of the risk scores. They’re not something that should factor in much with our current treatments. Some trials enroll patients with higher-risk disease, but the treatments are aimed at symptoms and enlarged spleens. Risk is something we consider, but it’s symptom presentation. It’s not so much driver mutation or risk but symptoms that drive what we’re trying to accomplish.

Within the NCCN Guidelines, with higher-risk or symptomatic lower-risk disease patients, we’re favoring JAK inhibitors. For the most part, we differentiate by platelet count. For greater than 50,000 platelets, we’re considering ruxolitinib or fedratinib, which are approved there. For less than 50,000 platelets, we’re favoring pacritinib, which has an accelerated approval in this markedly thrombocytopenic patient population. The 1 caveat—and something that’s overlooked a lot in the NCCN Guidelines—is the way it’s written. It seems as if any high-risk patient should receive ruxolitinib or fedratinib, but that excludes high-risk patients for whom anemia is their driving issue. If their main issue is anemia, and they don’t have much in the way of constitutional symptoms or symptomatic splenomegaly, then that patient probably isn’t a great candidate for a JAK inhibitor as an up-front treatment. That sometimes gets lost in the guideline, but there’s a drop-down as far as where to go when you’re considering directing your therapy at myelofibrosis-associated anemia as the prominent issue. That’s a bit separate.

When you look past first line in the NCCN Guidelines, anything is open. At that point, platelet thresholds don’t matter as much. Pacritinib can be considered as an option in the second-line setting. It’s interesting because it has an accelerated approval for fewer than 50,000 platelets, but there isn’t a completed trial focused on fewer than 50,000 platelets as the inclusion criteria for pacritinib. It’s been studied in any platelet count for fewer than 100,000. The ongoing study looks at fewer than 50,000, but it’s an effective agent regardless of platelet count. In that fewer than 50,000, the specific agent could be utilized. But in the second-line setting, it can be used there as well, just like fedratinib. If you started with fedratinib or pacritinib, dose-modified ruxolitinib could be a consideration in the second-line setting.

John O. Mascarenhas, MD: My understanding is that pacritinib also has this category 2b as an indication, even in up-front input accounts of greater than 50,000 platelets. Ruxolitinib remains category 1. That’s a nuance change in the guidelines.

Transcript edited for clarity.

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