Once-daily treatment with the oral JAK1/2 and ACVR1/ALK2 inhibitor momelotinib significantly improved outcomes of patients treated for myelofibrosis. Ruben Mesa, MD, FACP, and colleagues presented results of the MOMENTUM phase III randomized study, which evaluated momelotinib vs danazol in symptomatic and anemic patients with myelofibrosis previously treated with standard-of-care JAK inhibitor therapy, at the 2022 ASCO Annual Meeting (Abstract 7002).
Ruben Mesa, MD, FACP
Anemia and Myelofibrosis
In myelofibrosis, scar tissue forms in the bone marrow and hinders the body’s ability to produce healthy blood cells. Anemia is observed in virtually all patients with myelofibrosis and negatively impacts survival, Dr. Mesa said.
“A third of the patients have anemia upfront, and most patients will develop it over the course of their disease,” said Dr. Mesa, Executive Director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center. “For patients with severe anemia, survival is shortened to about 2 years. Even with mild anemia, the median survival is 4.9 years. A drug to treat anemia in these patients has been urgently needed.”
Without anemia, median survival with myelofibrosis is closer to 8 years, he clarified.
Myelofibrosis features abnormal signaling of JAK proteins and excessive activation of another protein, ACVR1. Pioneering myelofibrosis drugs developed over the last decade, such as ruxolitinib, inhibit the harmful JAK signaling, whereas momelotinib is the first drug that inhibits both JAK and ACVR1, Dr. Mesa said.
“It has JAK1, JAK2, and ACVR1 inhibitors in one drug, and addresses chronic inflammation due to the hyperactivation of ACVR1 as a consequence of the disease,” he explained.
Findings
MOMENTUM enrolled 195 patients in 21 countries. Of the enrolled participants, 130 received momelotinib and 65 received danazol. Participants did not know until after 24 weeks which drug they received, and those in the danazol group were allowed to cross over to receive momelotinib at that time.
In the momelotinib group:
- All prespecified primary and key secondary endpoints were met.
- Significant improvements in symptoms, spleen size, and anemia measures were observed.
- Favorable safety and a trend toward improved overall survival were documented.
- Participants required fewer transfusions to replace red blood cells and evidenced better oxygen-carrying hemoglobin levels.
“The results were compelling,” Dr. Mesa said. “The study enrolled participants entirely during the COVID-19 timeframe, which was remarkable. Momelotinib met all primary and secondary endpoints and within the short span of 6 months, there was a trend toward overall survival benefit, which is also remarkable.”
“Findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anemia,” Dr. Mesa concluded.
Disclosure: The MOMENTUM study was sponsored by Sierra Oncology. For full disclosures of the study authors, visit coi.asco.org.
