Bomedemstat in myelofibrosis: Phase I/II study results

Results from an open-label, phase I/II study (NCT03136185), evaluating bomedemstat, an irreversible lysine-specific demethylase 1 (LSD1) inhibitor, in 89 patients with myelofibrosis (MF) that is refractory or resistant to, inadequately controlled by, or intolerant to approved therapies, were published in Blood Advances by Gill et al. The primary objectives were to assess safety and tolerability and effects on spleen volume. Exploratory endpoints included hematologic response, patient-reported symptom burden, bone marrow fibrosis grade, and mutant allele frequency.

Key data: At data cutoff, 97% of patients had experienced ≥1 adverse event (AE) of any grade, and 69% experienced ≥1 Grade 3–5 AE. The most common AEs of any grade were thrombocytopenia (48%), dysgeusia (36%), anemia (33%), diarrhea (32%), and nausea (30%). Serious AEs (SAEs) were reported in 49% of patients, and 26% of patients discontinued treatment due to AEs. Treatment-related AEs (TRAEs) of any grade, Grade 3–5 TRAEs, and serious TRAEs were reported in 79%, 56%, and 14% of patients, respectively. At Week 24, 66% of patients had a reduction in spleen volume from baseline, and 26% had a reduction ≥20% (n = 35). Over 24 weeks, platelet and white blood cell counts normalized, and hemoglobin remained stable. Stable or improved bone marrow fibrosis was reported in 83% of patients (n = 35), and 56% of patients had reduced JAK2, CALR, or MPL variant allele frequency (VAF; n = 36) at 24 weeks.

Key learning: Bomedemstat demonstrated clinical activity, including splenic, symptomatic, and molecular responses, in patients with MF that is refractory or resistant to, inadequately controlled by, or intolerant to approved therapies, supporting its continued development in this population.