JAK Inhibitors in Patients With Cytopenic Myelofibrosis

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

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

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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: Let’s get back to our case. So this is the gentleman who’s symptomatic, big spleen, almost 150,000 hemoglobin, is close to 14, sees Kristen in Ann Arbor, and she starts him on 10 mg twice a day of ruxolitinib…. After 6 months, [she] ends up dose reducing to 5 mg twice daily, mainly because the cytopenia has become quite limiting, and we’ve all seen these kinds of cases where that can happen. The problem is, now he’s coming back and complaining about worsening fatigue [and] night sweats. His spleen is clearly bothering him, and today in the visit with Kristen, his platelet count is 46,000, the hemoglobin went from 14 to 12, he is feeling unwell, and he’s telling Kristen, “I just feel so fatigued. Maybe I need a transfusion.” What are you going to do with a patient like this? You’ve dosed reduced them, they’re feeling symptomatic, [and] their counts are now lower.

Kristen M. Pettit, MD: My first question, and it’s a very difficult question to answer, is whether the cytopenias and some of what he’s feeling [are] related to disease progression toxicities from the medication. I think that can be hard to parse out often. In his case, though, it sounds like his night sweats, abdominal pain—I assume that means his spleen is larger. It sounds to me like the disease is not well controlled with ruxolitinib and it’s not just a matter of drug-related hematologic toxicities. That’s obviously a worrisome sign. The other very worrisome sign is…that we’ve had to de-escalate the ruxolitinib dose because of this cytopenia down to 5 mg [twice daily]; that’s definitely a red flag in my mind. As we’ve mentioned a couple of times, I think dose intensity matters in myelofibrosis, and maximizing the dose of JAK inhibition that you can get into patients does matter. So lots of red flags here for possible disease progression or at least lack of disease control on his current JAK inhibitor. I think I would want to reassess the disease status, probably, as I mentioned before, do next-generation sequencing to see if there’s anything biologically that has changed or progressed since his disease phenotype has changed from a more proliferative to a more cytopenic disease. In the past, we may have considered trying to push through with ruxolitinib or something like that in a patient in this situation. But now we have another option for these patients with cytopenic MF [myelofibrosis], which is pacritinib, the newer JAK inhibitor that was approved in February 2022. At this point, I think there is plenty reason to switch agents, and pacritinib would be my go-to for all the benefits that Andrew just mentioned about pacritinib in cytopenic MF. The benefit of trying to maximize the JAK2 inhibition while minimizing the hematologic toxicities and trying to inhibit other pathways that might be now driving his disease, such as IRAK1 and maybe ACVR1. Although it doesn’t sound like he’s too anemic with that hemoglobin of 12, but it has been a reduction for him. That might be an added benefit, as well, if we could get that anemia a bit better tuned up. Then I think also, as we’ve been talking about, if he is a transplant candidate…circling back to that idea at this time would be appropriate too.

Transcript edited for clarity.