Dr Kishtagari on the Impact of Momelotinib on the Management of Anemic Myelofibrosis

Ashwin Kishtagari, MD, assistant professor of Medicine, Hematology and Oncology, Vanderbilt University Medical Center, discusses how momelotinib (Ojjaara) addresses unmet needs in the management of myelofibrosis following disease progression on ruxolitinib (Jakafi).

The JAK1/JAK2 and ACVR1 inhibitor momelotinib was granted FDA approval in September 2023 for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary or secondary myelofibrosis, and anemia based on findings from the phase 3 MOMENTUM trial (NCT04173494) and a subset of adult patients with anemia in the phase 3 SIMPLIFY-I trial (NCT01969838).

Anemia has been a long-standing unmet need in the management of myelofibrosis, Kishtagari begins. Ruxolitinib (Jakafi), the longest-standing JAK inhibitor in this space, is effective in improving symptoms and reducing splenomegaly. However, it frequently leads to the development of anemia, necessitating dose reductions, he explains. Despite these adjustments, many patients continue to experience persistent anemia, Kishtagari adds. Historically, there has been no specific agent to offer these patients, particularly those presenting with anemia at the time of diagnosis, as ruxolitinib is known to cause cytopenias, Kishtagari details.

During the ongoing search for an agent that could both improve hemoglobin levels and manage symptoms and splenomegaly, momelotinib emerged as a promising candidate, Kishtagari states. Clinical data have shown that momelotinib not only demonstrates comparable efficacy to other JAK inhibitors in reducing spleen volume and alleviating constitutional symptoms in anemic, symptomatic myelofibrosis but also effectively addresses disease-related anemia symptoms, he emphasizes. In MOMENTUM, patients with symptomatic and anemic myelofibrosis who were previously exposed to a JAK inhibitor experienced a higher reduction in tumor symptom score with momelotinib than danazol.

Overall, the approval of momelotinib represents a significant advancement in the myeloma treatment paradigm, providing a new option for managing both the disease and its associated anemia, Kishtagari concludes.