John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai, New York, NY, discusses MANIFEST (NCT02158858), an ongoing Phase II study evaluating the efficacy of the novel BET inhibitor pelabresib (CPI-0610) in JAK-inhibitor-naïve myelofibrosis patients. The study found that pelabresib is active as a monotherapy and in combination with ruxolitinib in both a salvage therapy and frontline therapy setting. High spleen volume and symptom response rates were seen in the frontline setting in particular. Almost 33% of patients experienced a reduction in bone marrow fibrosis, and an improvement in hemoglobin could be seen in anemic patients. Pelabresib was well tolerated, with most patients only experiencing low grade adverse events that could easily be managed. A planned Phase III study aims to improve overall quality of life, duration of response and overall survival in myelofibrosis patients. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.