Myelofibrosis Management: Current Treatment Guidelines

EP: 1.Identifying the Signs and Symptoms of Myelofibrosis

EP: 2.What is the Role of Cytogenetics/Genomics in Myelofibrosis?

EP: 3.Biomarkers in Myelofibrosis: LDH, BMF, and Triple-Negative Disease

EP: 4.Evolving Role of Transplantation in Myelofibrosis

EP: 5.Selecting Transplantation Versus Systemic Therapy in Myelofibrosis

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EP: 6.Myelofibrosis Management: Current Treatment Guidelines

EP: 7.Patient Scenario 1: A 72-Year-Old Man With Primary Myelofibrosis

EP: 8.Value of JAK Inhibitors in Myelofibrosis Management

EP: 9.JAK Inhibitors in Patients With Cytopenic Myelofibrosis

EP: 10.Myelofibrosis: Dosing JAK Inhibitors and Managing Adverse Events

EP: 11.Sequencing of JAK Inhibitors in Patients With Myelofibrosis

EP: 12.Patient Scenario 2: A 68-Year-Old Woman With Anemic MF

EP: 13.Key Takeaways: Optimal Use of JAK Inhibitors in MF and Future Directions in Care

EP: 14.JAK Inhibitors, Mutations, and Transplantation in Myelofibrosis Management

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.