A comprehensive review of the treatment landscape for myelofibrosis (MF) and recent ASCO and ASH data updates on JAK2 inhibitors.
Amer Zeidan, MBBS: Let’s pivot to myelofibrosis, which is another area where there has been a lot of progress. Many phase 3 trials are ongoing. Before we go into the ASH [American Society of Hematology Annual Meeting] abstracts, give us your thoughts about the field. What are the most important questions being addressed? How did the data presented at ASH answer some of those questions?
Rami Komrokji, MD: At ASH, there were more sessions for MPN [myeloproliferative neoplasm] than MDS [myelodysplastic syndrome] because there are a lot of trials and active drugs. Myelofibrosis is a tough disease to treat. We’ve made some progress with JAK2 inhibitors in the management of splenomegaly and constitutional symptoms by improving the patient’s survival, but many patients have suboptimal response, treatment failure, and cytopenias, which are an unmet need in patients with myelofibrosis. The other area that’s an unmet need is the accelerated phase, or when this progresses to acute myeloid leukemia.
Obviously, we have 3 JAK2 inhibitors approved by the FDA available. Ruxolitinib has been the backbone, or the first JAK2 that we’ve used for many years. That does a great job in patients with proliferative disease in controlling spleen symptoms, indirectly improving patient survival. Fedratinib has a similar profile, and it could probably be used as a second line in proliferative myelofibrosis after ruxolitinib failure. Pacritinib is the latest approval that has JAK2 and IRAK1 activity. It’s niche and used in patients with low platelets for whom you don’t have to do dose reduction. It’s approved by the FDA for patients with platelets less than 50 per mm3. The NCCN [National Comprehensive Cancer Network] Guidelines also incorporate that, and it can be used as a second line regardless of the platelet count.
Some data at ASH looked at pacritinib’s impact on anemia, and there could be a hematologic improvement. Some patients who are transfusion dependent become independent, and the other—in patients who were transfusion independent, a higher rate of them stayed independent through a mechanism of action working on the ACVR receptor. This is similar to what was presented with momelotinib, which is the fourth JAK2 inhibitor that finished a phase 3 trial, which was originally presented at ASCO [American Society of Clinical Oncology Annual Meeting]. Dr [Aaron] Gerds presented an update at ASH from the MOMENTUM study, looking at momelotinib vs danazol in patients after first-line failure, showing improvement in spleen, symptoms, and anemia response. We anticipate that this drug will be available for patients sometime during mid-2023.
Transcript edited for clarity.