Clinical trial round-up: Treating anemia in patients with myelofibrosis

The MPN Hub was pleased to speak to Aaron Gerds, Cleveland Clinic Taussig Cancer Institute, Cleveland, US. Gerds discussed current and emerging treatments for anemia in patients with myelofibrosis (MF).

Gerds highlights the impact of anemia on survival outcomes in patients with MF, and reviews key data from the phase II ACE-536-MF-001 trial (NCT03194542) evaluating the safety and efficacy of luspatercept in patients with MF and anemia, including patients with and without transfusion dependence and concurrent Janus kinase (JAK) inhibition. He then highlights the ongoing randomized, phase III INDEPENDENCE trial (NCT04717414) assessing the safety and efficacy of luspatercept in combination with ruxolitinib in transfusion-dependent patients with MF. Finally, Gerds discusses potential future combinations of luspatercept with ACVR1 inhibitors.

Key learnings

• Around 40% of patients with MF have anemia at diagnosis, and over the first year since diagnosis, 60% of patients will develop anemia.¹
• Anemia is associated with worse outcomes in patients with MF and can impact the quality of life of the patient.¹
• Transfusion-dependent patients with MF have lower survival rates than transfusion-independent patients.¹
• Luspatercept is an activin receptor ligand trap that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with myelodysplastic syndromes and beta thalassemia.²
• The phase II ACE-536-MF-001 trial evaluated the safety and efficacy of luspatercept in patients with MF.³
  • This trial consisted of four major cohorts: patients who were receiving ruxolitinib and transfusion-independent; patients who were receiving ruxolitinib and transfusion-dependent; patients who were not receiving ruxolitinib and transfusion-independent; and patients who were not receiving ruxolitinib and transfusion-dependent.
  • Luspatercept improved anemia in all cohorts, with improved hemoglobin levels in patients who were transfusion-independent, and patients who were transfusion-dependent becoming transfusion-independent.
  • Patients receiving concurrent ruxolitinib and who were transfusion-dependent had the largest number of responses, with 30% of patients becoming transfusion-independent for at least a 12-week period, and 50% of patients had their transfusion burden halved.
  • The most common adverse events were hypertension, diarrhea, headaches, and bone pain, with no additive toxicity when combining luspatercept with ruxolitinib.
• Results from the ACE-536-MF-001 trial served as the basis for the ongoing randomized phase III INDEPENDENCE trial of luspatercept in combination with ruxolitinib in transfusion-dependent patients with MF.
• Luspatercept is now included in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of anemia in patients with MF.⁴
• Combining luspatercept with ACRV1 inhibitors, such as momelotinib and pacritinib, may have a synergistic effect, and clinical trials evaluating these combinations are in development.

This educational resource is independently supported by Bristol Myers Squibb. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.