Dr Parrondo on the Clinical Benefit of Momelotinib on Anemia in Myelofibrosis

Ricardo D. Parrondo, MD, hematologist/oncologist, assistant professor, Mayo Clinic, discusses the clinical benefit seen with momelotinib (Ojjaara) in anemic myelofibrosis, and where it fits into the current treatment paradigm in this disease landscape.

On September 15, the JAK1/JAK2 and ACVR1 inhibitor momolotinib was granted FDA approval 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-1 trial (NCT01969838).

In MOMENTUM, 25% of patients with symptomatic and anemic myelofibrosis who were previously exposed to a JAK inhibitor experienced a 50% or greater reduction in tumor symptom score (TSS) with momelotinib vs 9% in the danazol arm (P = .0095). Furthermore, 30% of patients in the momelotinib arm achieved red blood cell transfusion independence (P = .023) compared with 20% treated with danazol. Momelotinib also led to a reduction in spleen volume and an improvement in anemia-related symptoms. Importantly, momelotinib had low rates of anemia and thrombocytopenia, Parrondo details, suggesting it may stabilize or enhance anemia and could be safely administered even to patients with low platelet counts.

Similarly, data from the anemic subset in the SIMPLIFY-1 trial demonstrated that 31.4% of patients treated with momelotinib achieved a spleen volume reduction of at least 35% vs 32.6% with ruxolitinib. A a numerically lower percent of patients treated with momolotinib (25%) experienced a reduction in TSS of 50% or more at week 24 compared with ruxolitinib (36%).

Comparison between ruxolitinib and momolotinib shows that ruxolitinib may be more effective in managing symptoms and reducing spleen volume, Parrondo says. However, Parrondo states that momolotinib is the preferred choice for patients primarily struggling with anemia and requiring transfusions, noting that ruxolitinib is known to potentially induce cytopenias and might pose challenges for individuals with thrombocytopenia or anemia.

Momolotinib not only demonstrates comparable efficacy in reducing spleen volume and alleviating constitutional symptoms in anemic, symptomatic myelofibrosis compared to available JAK inhibitors, but the agent also has the potential to effectively address disease-related anemia symptoms, which standard-of-care agents currently fall short of achieving.

Although it may not achieve the same level of spleen reduction and symptom control as ruxolitinib, momolotinib offers extends the benefits of JAK inhibition to patients with a longstanding unmet need.