Sequencing of JAK Inhibitors in Patients With Myelofibrosis
In light of the current treatment armamentarium for myelofibrosis, key opinion leaders in the field discuss optimal sequencing of available JAK inhibitors.
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.
