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Pelabresib + ruxolitinib is a combination therapy currently evaluated for the treatment of myelofibrosis in patients who have not previously received a JAK inhibitor. Pelabresib is an oral, small molecule inhibitor of bromodomain and extraterminal domain (BET) proteins, targeting epigenetic regulation of genes involved in inflammation and fibrosis. Ruxolitinib is an oral, small molecule inhibitor of Janus kinase 1 and 2 (JAK1, JAK2), blocking pro-inflammatory signaling pathways. The dual inhibition demonstrated additive benefits in clinical trials, significantly increasing spleen volume reduction, improving symptom scores, and potentially modifying disease biology by reducing pro-inflammatory cytokine levels and improving bone marrow morphology compared with ruxolitinib alone[1][2][3][4][5][6].
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