The targeted therapy momelotinib may offer clinically significant improvement in disease-related symptoms, including anemia and spleen enlargement, for patients with myelofibrosis, according to a novel study published by Srdan Verstovsek, MD, PhD, and colleagues in The Lancet.
The findings support the use of momelotinib—a potent ACVR1/ALK2 and JAK1/2 inhibitor—over the standard therapy danazol in treating patients with myelofibrosis who were resistant, refractory, or intolerant to first-line therapy—especially patients who were symptomatic and those with anemia.
Srdan Verstovsek, MD, PhD
Background
Myelofibrosis, a type of myeloproliferative neoplasm, is characterized by dysregulated JAK signaling—which can disrupt the body’s normal production of blood cells and can lead to common symptoms such as an enlarged spleen and anemia. Chronic anemia in these patients is associated with poor prognoses.
Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anemia. In this trial, momelotinib improved anemia and reduced transfusion dependency in patients with myelofibrosis who were previously treated with JAK inhibitors. Momelotinib can be administered and maintained at full dosage because it does not suppress bone marrow activity like other JAK inhibitors.
“Current options for managing anemia in our patients [with myelofibrosis] provide only modest and temporary benefits, so we are excited about these findings,” explained lead study author Dr. Verstovsek, the United Energy Resources, Inc, Professor of Medicine and Director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “The trial results suggest that momelotinib is safe, well-tolerated, and can improve one of the most common and debilitating clinical problems for this patient population,” he highlighted.
KEY POINTS
- After 24 weeks, 25% of patients taking momelotinib experienced symptom reduction vs 9% of patients taking danazol.
- A response rate of 25% for spleen reduction was seen for patients receiving momelotinib.
- Patients who received momelotinib required less blood transfusions than those receiving danazol.
MOMENTUM: Study Methods and Results
The new study—one of the first of its kind to evaluate JAK1/2 and ACVR1/ALK2 inhibition in patients with myelofibrosis and anemia—was designed to compare the clinical benefits of momelotinib with those of danazol, a synthetic androgen currently used to treat anemia in patients with symptomatic myelofibrosis.
In the international, randomized phase III MOMENTUM trial, researchers randomly assigned 195 adult patients to receive either momelotinib plus placebo (n = 130) or danazol plus placebo (n = 65). Among the trial participants, 63% of them identified as male and 37% identified as female. The participants for both groups had a median age of 71 to 72 years.
The trial’s primary endpoint was symptom reduction after 24 weeks of treatment, defined as a 50% or greater reduction in the Myelofibrosis Symptom Assessment Form Total Symptom Score. The researchers discovered that 25% of patients who received momelotinib saw benefits in their disease symptoms compared with 9% of those who received danazol.
Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared with those receiving danazol.
Conclusions
The safety profile of momelotinib was comparable to the safety observed in previous clinical trials. The most common nonhematologic side effects experienced by trial participants in the momelotinib group included diarrhea, nausea, weakness, and itchy or irritated skin.
“If approved, momelotinib could offer an effective option for patients with myelofibrosis to improve anemia, splenomegaly, and other disease-related symptoms over other approved medications so far,” Dr. Verstovsek emphasized. “Momelotinib may also be an ideal partner for combinations with other investigational agents in development to further control myelofibrosis symptoms,” he concluded.
The researchers noted that they continue to monitor the effectiveness of momelotinib through ongoing patient follow-ups and long-term survival.
Disclosures: The research in this study was supported by Sierra Oncology. For full disclosures of the study authors, visit thelancet.com.
