Dr Gangat on JAK Inhibitor Selection in Treatment-Naive Myelofibrosis

Naseema Gangat, MBBS, hematologist, oncologist, education chair and program director, Division of Hematology, Department of Medicine, Mayo Clinic Rochester, provides insight into the clinical utility of momelotinib (Ojjaara) and expands on JAK inhibitor selection for patients with treatment-naive myelofibrosis.

Gangat highlights the functionality of momelotinib in addressing both spleen symptoms and total symptom score. She notes that the agent can also have activity against anemia, which presents a significant advantage over other previously favored JAK inhibitors, such as ruxolitinib (Jakafi). In September 2023, the FDA approved momelotinib for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.

When choosing a JAK inhibitor in the frontline setting for patients with myelofibrosis, momelotinib could be the preferred option for those with borderline hemoglobin levels—such as approximately 10 to11 g/dL—prominent spleen enlargement, and symptoms, according to Gangat. In a patient with borderline hemoglobin, starting with ruxolitinib could exacerbate anemia, which could adversely affect the patient's quality of life, she adds.

Although the approval of momelotinib was a significant development in myelofibrosis treatment, unmet needs still exist for this patient population, Gangat continues. For the subset of patients who do not experience an improvement in anemia when treated with momelotinib, improved treatment options are needed, she says.

Additionally, retrospective comparisons between patient outcomes on ruxolitinib and momelotinib in clinical trials conducted at the Mayo Clinic revealed superior drug retention rates with momelotinib. Specifically, drug survival data indicate that at the 10-year mark, approximately 7% of patients treated with momelotinib were still on therapy, whereas a higher discontinuation rate was observed with ruxolitinib, primarily attributed to anemia-related adverse effects, she says.

Gangat suggests that while momelotinib offers a valuable treatment alternative over with benefits in symptom control and anemia management, further exploration and development of treatments that can fully address the spectrum of myelofibrosis symptoms and complications are still required.