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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
To download this visual abstract, click belowDownload here
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Inhibiting the Janus kinase (JAK) pathway is considered the hallmark in treating myelofibrosis (MF); however, treatment discontinuation due to adverse events has been a concern. After JAK failure, therapeutic...
Interim translational data from the MANIFEST phase II study of pelabresib in myelofibrosis
Myelofibrosis (MF) is characterized by abnormal megakaryopoiesis and overproduction of proinflammatory cytokines, which lead to bone marrow fibrosis,...
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