Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia. in Blood advances / Blood Adv. 2026 May 26;10(10):3494-3504. doi: 10.1182/bloodadvances.2025017575.

2026
AOU Alessandria

Tipo pubblicazione

Multicenter Study

Autori/Collaboratori (22)Vedi tutti...

Gill H
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Palandri F
lstituto di Ematologia "Seragnoli," Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Ross DM
Department of Haematology, Royal Adelaide Hospital and SA Pathology, Adelaide, SA, Australia.

et alii...

Abstract

Novel treatments that can improve outcomes of essential thrombocythemia (ET) are needed. In a phase 2 trial, participants with ET who required cytoreduction and had inadequate response to, or were intolerant of, ?1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200 × 109/L to 400 × 109/L). Primary end points were safety and response, defined as a platelet count of ?400 × 109/L without new thromboembolic events. Of 73 who received bomedemstat, at 24 weeks, 49 of 64 evaluable participants (77%) achieved a response. Durable reductions in platelet count (?400 × 109/L for ?12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10 × 109/L for ?12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10 × 109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ?1 thrombotic event, and 15 of 73 (21%) experienced ?1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. This trial was registered at www.clinicaltrials.gov as #NCT04254978.

Accesso banca dati bibliografica

PMID : 41758981

DOI : 10.1182/bloodadvances.2025017575

Keywords

Humans; Thrombocythemia, Essential/drug therapy/genetics; Female; Male; Platelet Count; Aged; Middle Aged; Receptors, Thrombopoietin/genetics; Janus Kinase 2/genetics; Adult; Treatment Outcome; Aged, 80 and over; Benzamides; Piperazines; Triazoles;