Lucia Masarova, MD
Lucia Masarova, MD, Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, said the updated long-term data for momelotinib show “durable efficacy and exciting outcomes” in patients with myelofibrosis, regardless of prior exposure to ruxolitinib.1,2
“We were thrilled to see ongoing and long-lasting improvements in myelofibrosis-related symptoms and splenomegaly, especially in patients after ruxolitinib failure. However, the most impressive clinical benefit of momelotinib stems from its effect on anemia, which gives this agent a truly special designation,” Dr. Masarova said.
“Achieving transfusion independence, or even considerably decreasing the burden of transfusions, often translates into improved quality of life and offers enormous benefit for these patients. Seeing the achievement of transfusion independence in 40% of patients who failed to respond to ruxolitinib is even more important, as anemia is the leading cause of ruxolitinib discontinuation and predicts worse outcome,” she continued.
Dr. Masarova also emphasized the “appealing” survival analysis, showing that median overall survival was not reached at 4.5 years for ruxolitinib-naive patients originally randomly assigned to momelotinib. This compares favorably to survival from pivotal ruxolitinib studies, she said, where the 3-year survival rate was approximately 78%.
“Even more exciting was the observed median survival of close to 35 months after ruxolitinib failure, which we have never seen before, suggesting this is an effective subsequent therapy that is so much needed for these patients,” she added.
Looking ahead, Dr. Masarova expects positive results from the currently enrolling phase III MOMENTUM study comparing momelotinib with danazol in anemic patients with myelofibrosis who failed to respond to ruxolitinib. She believes the study “will almost certainly highlight momelotinib’s benefits and hopefully lead to its approval.”
Given that momelotinib dosing is not limited by myelosuppression, Dr. Masarova predicted it could be an ideal candidate for combinational approaches in the future, especially with non-JAK–targeting agents, such as antifibrotics, bromodomain inhibitors, and even checkpoint inhibitors. Its longer tolerance and easier dose intensification, she added, might also play a vital role in preventing or abating emerging treatment resistance.
DISCLOSURE: Dr. Masarova reported no conflicts of interest.
1. Verstovsek S, Egyed M, Lech-Maranda E, et al: Robust overall survival and sustained efficacy outcomes during long term exposure to momelotinib in JAK inhibitor naive and previously JAK inhibitor treated intermediate/high risk myelofibrosis patients. 2020 ASH Annual Meeting & Exposition. Abstract 54. Presented December 5, 2020.
2. Harrison CN, Vannucchi AM, Platzbecker U, et al: Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): A randomised, open-label, phase 3 trial. Lancet Haematol 5:e73-e81, 2018.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Treatment with the novel JAK inhibitor momelotinib led to long-term overall survival and sustained transfusion independence in patients with intermediate- or high-risk myelofibrosis, according to updates from the SIMPLIFY-1 and SIMPLIFY-2 trials presented at the 2020 American Society of Hematology...