Sequencing of JAK Inhibitors in Patients With 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

EP: 9.JAK Inhibitors in Patients With Cytopenic Myelofibrosis

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

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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: We’ve talked a lot about the various benefits of JAK [Janus kinase] inhibitors. Gabby, we’ve got 3, maybe 4 JAK inhibitors approved. Do you find it a little strange that we’re able to sequence these JAK inhibitors using the same drug from the same class? It’s unusual in oncology; usually, you would pick a different mechanism of action. Any thoughts about why that might be or any evidence that suggests that there may even be molecular predictors, etc?

Gabriela S. Hobbs, MD: That’s a good question. I think, to some degree, yes, we can sequence, and it is surprising. As we’ve learned more about the JAK inhibitors, they definitely hit the kinases a bit differently. Therefore, in that regard, it makes sense that you could sequence and block the JAK-STAT [signal transducer and activator of transcription] signaling pathway that you weren’t able to block with the prior JAK inhibitor. It also makes sense, when you’re thinking about switching from a JAK inhibitor that’s more [of a] JAK1, JAK2 inhibitor to one of the newer JAK inhibitors, like pacritinib, that doesn’t do JAK1 that much but does IRAK1 [interleukin-1 receptor-associated kinase 1] and ACVR1 [activin A receptor type I], that you would have another benefit, or you would have a new response where you lost a response previously. Understanding those mechanisms of actions of each of the JAK inhibitors can help understand why you can quote-unquote “salvage” some of those patients or have a response in the second- or perhaps third-line setting. If the treatment goal is to improve splenomegaly, and transplant is not the goal, it’s nice to know that we can do that. However, if the goal is to get to transplant, knowing that you are able to successfully sequence one patient from one JAK inhibitor to another shouldn’t make you lose track of your objective. That is a person who should be [setting off] a lot of alarm bells. If you’re losing your response to a JAK inhibitor, spleens growing back, symptoms are coming back, or counts are looking much worse, that’s not a time to try to switch from one drug to the other, but a time to get that person to transplant if that hadn’t been part of the conversation.

Transcript edited for clarity.