General Updates | Managing splenomegaly in patients with myelofibrosis

Splenomegaly in patients with myelofibrosis is one of the major issues that, A, brings them to the attention of the physician initially. This is often how patients are diagnosed. For those patients that are known to have myelofibrosis, this is a major symptom and a major effect on their quality of life. For those patients that have massive splenomegaly, it affects their ability to eat, they have early satiety. It can have an effect on their blood countsm, make them more cytopenic by pulling all the blood into the spleen. They also are uncomfortable and have abdominal pain: potentially nausea, diarrhea, things like that, so obviously a major problem for patients with PV.

Luckily, these days we do have excellent medications to help patients control splenomegaly and symptoms related to splenomegaly. These are JAK inhibitors. We’ve had ruxolitinib now for many years, and it has been shown to be very effective in controlling splenomegaly. Usually, there’s some dose effect. A higher dose of ruxolitinib is more likely to have more of an effect on splenomegaly in these patients. Typically, anywhere from 10 to 15 milligrams twice a day of ruxolitinib will control/will cause decrease in the size of the spleen in most patients with myelofibrosis, which will result in improvement in their symptoms directly related to splenomegaly and other systemic symptoms as well, of course; will often allow them to be able to have better nutritional status and potentially contributes to their overall quality of life improvement as well as potentially overall survival that is seen with ruxolitinib. This is the drug that we’ve had available the longest. We now also have fedratinib: of course, another JAK inhibitor, which is also effective as a frontline therapy and potentially as a second-line agent after ruxolitinib, whether it’s due to intolerance of ruxolitinib, failure, also very effective in reducing the size of the spleen and controlling the symptoms related splenomegaly. Most recently, we also have pacritinib that was approved. Pacritinib is specifically more useful in patients that have cytopenic myelofibrosis, meaning they have low blood counts. Both fedratinib and ruxolitinib can be difficult to dose for those patients that have low platelets/low hemoglobin, especially low platelets. Pacritinib is an attractive option for these patients who have potential platelets less than 58,000 and who’s anemia may be more of a concern, and who still have significant splenomegaly that’s causing symptoms. Again, from using pacritinib, we would expect reduction in spleen size without compromising platelet counts and hemoglobin to the same extent that fedratinib and ruxolitinib do. It’s a nice potential option for those patients that have low blood counts.