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ASCO 2025 | An overview of novel JAKis in myelofibrosis: which patients benefit from pacritinib & momelotinib?
Andrew Kuykendall, MD, Moffitt Cancer Center, Tampa, FL, provides an overview of novel JAK inhibitors (JAKis) for the treatment of myelofibrosis. Dr Kuykendall highlights that while ruxolitinib has been a standard treatment for myelofibrosis, it can exacerbate anemia and thrombocytopenia, leading to treatment discontinuation. In contrast, novel JAKis such as pacritinib and momelotinib offer similar benefits with fewer side effects, providing an alternative treatment option for patients. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Novel JAK inhibitors in myeloproliferative neoplasms. So specifically when we think about myelofibrosis, our old standard has been ruxolitinib. This was approved back in 2011, very good at controlling disease-related symptoms and splenomegaly in patients with myelofibrosis. Unfortunately, it exacerbates anemia, often leads to low platelets, and this can be really challenging in patients that have a disease where they’re often anemic when they show up...
Novel JAK inhibitors in myeloproliferative neoplasms. So specifically when we think about myelofibrosis, our old standard has been ruxolitinib. This was approved back in 2011, very good at controlling disease-related symptoms and splenomegaly in patients with myelofibrosis. Unfortunately, it exacerbates anemia, often leads to low platelets, and this can be really challenging in patients that have a disease where they’re often anemic when they show up. We know in the real world, the development of anemia and thrombocytopenia is a common reason patients have to stop ruxolitinib altogether. And so in the last few years, we’ve actually developed these novel JAK inhibitors such as pacritinib or momelotinib that have the ability to provide some of the same benefits as ruxolitinib in terms of spleen volume reduction, disease-related symptom improvement, yet they don’t seem to cause the same anemia and thrombocytopenia.
In the setting of pacritinib, this actually got an accelerated approval for patients that have myelofibrosis and marked thrombocytopenia based on the results of the PERSIST-2 study, where patients that had low platelets were randomized to receive either pacritinib or best available therapy, and those that went on pacritinib had a better improvement in their spleen and quality of life than those that were treated with best available therapy.
Momelotinib was approved on the heels of the MOMENTUM study, which took patients who’d previously been on ruxolitinib, were anemic, had splenomegaly, and had symptoms, and randomized patients to either receive momelotinib or danazol. There, we saw momelotinib was associated with more improvement in symptoms, improvement in spleen volume reduction, improvement in quality of life, and actually decreased transfusion requirements. And so momelotinib really does represent an option for those patients that are struggling with anemia and myelofibrosis and it’s approved as such.
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