Selection and management of JAK inhibitor therapy in MF


Stephen T. Oh, MD, PhD: When it comes to the choice of JAK inhibitors available, we have ruxolitinib, which has been available for over a decade; federatinib, which was approved a few years ago; and pacritinib, which was recently approved. We have 3 JAK inhibitors available. They are similar in that they are all JAK inhibitors, but they are also somewhat distinct in some ways. For example, federatinib is a bit more specific for JAK2, but it also inhibits FLT3. Since FLT3 is an additional target, this means the drug is associated with certain gastrointestinal disorders [gastrointestinal] side effects: nausea, diarrhea, etc. The same is true with pacritinib which also inhibits JAK2 and FLT3.

In the case of federatinib, it is approved for use in first- or second-line myelofibrosis. But in my experience, it is particularly positioned as an option after patients have been treated with ruxolitinib. If they have a problem with ruxolitinib or after getting an initial response to ruxolitinib, if their symptoms or spleen grows back, the choice of federatinib is particularly appropriate. pacritinib, [which has just been] recently approved, is a unique drug among the 3 JAK inhibitors that are now available. It doesn’t really cause significant thrombocytopenia, and it’s been specifically studied in patients with severe thrombocytopenia with an FLT3 count below 50. That’s where using something like ruxolitinib or fedratinib doesn’t is not possible because, in particular with ruxolitinib, the reduction in the number of platelets is a problem in terms of obtaining an effective dose of ruxolitinib in patients with severe thrombocytopenia. In contrast, pacritinib can be used in patients with very low platelet counts. This is precisely what the FDA approval was for: patients with platelet counts below 50 per mm3.

Ruben Mesa, MD: The side effect profile of each JAK inhibitor is slightly different. With federatinib, we monitor for cytopenias, gastrointestinal adverse events, and the rare issues of Wernicke’s encephalopathy or thymine deficiency. With ruxolitinib, there may be cytopenia, anemia, or thrombocytopenia, but this is the main dose-limiting toxicity. There may be an increase in liver function tests. There is an increased risk of non-melanoma skin cancers, as well as an increase in the herpes zoster virus. I will frequently consider having people receive the inactivated shingles vaccine as part of taking the medication. Similarly, although pacritinib is safe for people with thrombocytopenia, cytopenias can still occur, although [that is] minus one factor. There may be gastrointestinal side effects, as there may be with fedratinib, so we will usually have patients on antinausea medication and antidiarrheals so we can monitor as needed. In trials, if individuals are thrombocytopenic and at risk of bleeding, we continue to monitor all of that closely, as well as cardiovascular risk. The studies do not suggest that there is any additional risk from the drug, but it is generally a fairly high risk group of individuals. These things need to be watched carefully.

Transcript edited for clarity.

Martin E. Berry