Dr Kuykendall on the Advantages of Treatment With Momelotinib in Myelofibrosis

“Momelotinib can do what other JAK inhibitors can do, which is improve splenomegaly and disease-related symptoms. Overall, it is well tolerated, too. However, momelotinib tends to—likely through its ability to inhibit ACVR1—lead to more available iron use, which can get rid of the anemia that goes along with myelofibrosis. That’s the advantage.”

Andrew Kuykendall, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the advantages of treatment with momelotinib (Ojjaara) over older-generation JAK inhibitors in myelofibrosis.

Momelotinib offers a unique advantage among JAK inhibitors by addressing both splenomegaly and disease-related symptoms while also improving anemia in patients with myelofibrosis, Kuykendall begins. Like other JAK inhibitors, it effectively reduces spleen volume and alleviates symptoms, but it stands out due to its favorable tolerability profile, with fewer gastrointestinal adverse effects compared with agents like pacritinib (Vonjo) and fedratinib (Inrebic).

The distinguishing feature of momelotinib is its ability to inhibit ACVR1, a key modulator of hepcidin, which is involved in iron metabolism. By suppressing hepcidin, momelotinib increases the availability of iron for erythropoiesis, thereby alleviating anemia, Kuykendall explains. Anemia affects nearly all patients with myelofibrosis during their disease course, and managing this condition without exacerbating it is a critical goal in treatment, he emphasizes. Decreasing anemia also reduces the need for blood transfusions, which can significantly enhance a patient’s quality of life by minimizing the burden of frequent blood work and transfusion-related health care visits, Kuykendall notes.

Although highly effective, standard ruxolitinib (Jakafi) is often associated with a decline in hemoglobin levels, particularly early in treatment, Kuykendall says, explaining that this can be problematic for patients presenting with baseline hemoglobin levels near the threshold for transfusion dependence. Starting these patients on ruxolitinib may increase the risk of requiring transfusions, which can negatively affect quality of life despite the drug’s efficacy in controlling splenomegaly and symptoms, he states.

Overall, momelotinib provides an effective alternative to other available agents in myelofibrosis, especially for patients at risk of or experiencing significant anemia, Kuykendall concludes.