Visual abstract | MANIFEST trial: Updates from the EHA 2022 Congress

During the European Hematology Association (EHA) 2022 Congress, Claire Harrison¹ presented the latest results from the ongoing, open-label phase II MANIFEST trial (NCT02158858) investigating pelabresib, a bromodomain and extraterminal (BET) protein inhibitor in myelofibrosis (MF) and essential thrombocytopenia (ET).¹ The study comprises four study arms: pelabresib monotherapy in MF and ET (Arms 1 and 4, respectively), pelabresib add-on to ruxolitinib in patients with MF with suboptimal response or MF progression (Arm 2), and pelabresib in combination with ruxolitinib in Janus kinase inhibitor (JAKi)-naïve patients with MF (Arm 3).¹

Harrison focused on results from Arms 2 and 3, which are summarized on the visual abstract below. Pelabresib was associated with bone marrow improvements which were determined by a decrease in megakaryocyte clusters (that correlated with SVR35 response), reduced reticulin density, and an increase in erythrocytes. There were also rapid (14 days) and durable (through 24 weeks) decreases in plasma levels of NF-κB targets and inflammation-related cytokines during the treatment.¹