Pharmacologic management of ET: established therapies and emerging agents

Essential thrombocythemia (ET) is a chronic Philadelphia-negative myeloproliferative neoplasm defined by sustained thrombocytosis and a propensity for both thrombotic and hemorrhagic events. Although overall survival for ET approximates that of age-matched controls, morbidity from vascular complications and long-term transformation to myelofibrosis or acute leukemia underscores the need for individualized, risk-adapted pharmacotherapy. Areas covered: Drawing on recent clinical trials, expert consensus, and emerging data presented at hematology meetings (2018–2025), we highlight established cytoreductive strategies–hydroxyurea, interferon-α (including pegylated formulations), and anagrelide–and evaluate emerging targeted agents. Key trials include the phase 2 LSD1 inhibitor bomedemstat trial showing significant platelet-count reduction and mutation-burden improvement the phase 3 SURPASS-ET trial comparing ropeginterferon alfa-2b versus anagrelide, ongoing investigations of JAK–STAT pathway modulators, and emerging data on the anti-calreticulin (CALR) monoclonal antibody INCA033989, which selectively targets mutCALR progenitors to suppress malignant hematopoiesis while sparing normal hematopoiesis. Expert opinion: Future advances in ET management hinge on integrating molecular risk stratification into treatment algorithms, optimizing combination regimens to deepen molecular remissions, and prioritizing agents with favorable safety profiles. Personalized approaches leveraging allele-burden dynamics and symptom-control metrics are likely to define the next era of ET pharmacotherapy.