Clinically significant improvements in myelofibrosis-associated symptoms, anemia, and spleen response were achieved with momelotinib, compared with danazol, in patients with myelofibrosis. These findings were published in The Lancet.
Danazol has often been used to treat patients with myelofibrosis, which results in symptom and spleen improvements but does not address anemia. However, momelotinib, a JAK1/JAK2 inhibitor that also inhibits ACVR1, has demonstrated symptom, spleen, and anemia benefits in patients with myelofibrosis.
A group of researchers compared momelotinib with danazol in JAK-inhibitor-exposed, symptomatic patients with anemia and intermediate-risk or high-risk myelofibrosis, with the goal of confirming the differentiated clinical benefits. Their findings were published in The Lancet.
The participants were part of the international, double-blind, randomized, controlled, phase 3 MOMENTUM study. Of the 195 patients, 130 (67%) received momelotinib 200 mg orally once a day and a danazol placebo (momelotinib group) and 65 (33%) received danazol 300 mg twice a day and a momelotinib placebo (danazol group). Treatment was for a 24-week period.
The primary endpoint for this study was the total symptom score (TSS) response rate at week 24 via the Myelofibrosis Symptom Assessment Form. More patients in the momelotinib group reported at least a 50% reduction in TSS than did patients in the danazol group: 25% vs 9%. The researchers wrote that this showed the superiority of momelotinib treatment with regard to the primary endpoint.
The researchers concluded that “Treatment with momelotinib was associated with clinically significant improvements in myelofibrosis-associated symptoms, anemia measures, and spleen size, with favorable safety compared with danazol in symptomatic patients with anaemia and previous JAK inhibitor exposure,” concluded the researchers.
“These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anemia.”
The researchers also noted another key benefit of momelotinib treatment. Patients were able to tolerate higher doses of momelotinib due to reduced myelosuppressive activity.
Limitations to the study include a lack of a direct, long-term comparison of survival between the 2 treatment groups. The researchers also reported a potential concern regarding early discontinuation in patients with advanced, symptomatic anemic myelofibrosis. But most patients in both groups were able to complete the treatment period.
Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Verstovsek S, Gerds AT, Vannucchi AM, et al; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (Momentum): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0