Bomedemstat May Provide Symptom Relief and Disease-Modifying Action for Advanced MF

The combination of bomedemstat and ruxolitinib (RUX) showed promising tolerability in first- and second-line myelofibrosis (MF) treatment, with reductions in symptoms and spleen size. Mutant allele frequency and bone marrow fibrosis improvements were observed.

Harinder Gill, MBBS, MD, The University of Hong Kong, presented the results of this ongoing, phase 2, open-label trial. Treatment with RUX is the standard of care for patients with advanced MF; however, most patients have poor survival rates and discontinue treatment. ¹ Bomedemstat is a lysine-specific demethylase-1 inhibitor with evidence of safety and tolerability as a monotherapy for MF.² Dr Gill and colleagues wanted to evaluate the safety and tolerability of bomedemstat as an add-on to RUX for patients with relapsed or refractor MF   during treatment with RUX (cohort A) or in a front-line setting for patients who are Janus kinase (JAK) inhibitor naive (cohort B). Cohort A (n=30) continued their previous dose of RUX, and cohort B (n=13) started at 10 mg twice daily. Both cohorts started receiving bomedemstat at 0.4 mg/kg/day.

Throughout the trial, hemoglobin concentration and platelet count remained stable. Most adverse effects (AEs) were grade 1 or 2. The main AEs were anemia (20.9%) and thrombocytopenia (16.2%). Other AEs included constipation (18.6%), diarrhea (30.2%), and edema (25.5%). The total symptom score was assessed based on the MF symptom assessment form. In cohort A, 26.9% of patients had a greater than 50% reduction in symptoms, and in cohort B, 33.3% experienced that level of symptom reduction. Spleen volume reduction (>35%) was observed in 9.1% of cohort A and 38.5% of cohort B.

In addition, some patients were able to become transfusion independent. Of four transfusion-dependent patients, one became transfusion independent. Of 11 transfusion-requiring patients, five became transfusion independent. As exploratory endpoints, the investigators looked at changes in mutant allele frequencies. Seventeen of the 30 patients experienced reductions in the JAK2 variant allele frequency; of those 17, 10 experienced bone marrow fibrosis reduction.

“The combination of bomedemstat with ruxolitinib is safe and tolerable in the first and second-line setting,” Dr Gill concluded, pointing out there was also “evidence of disease modifications.”

REFERENCES

1 Palandri F, Breccia M, Bonifacio M, et al Life after ruxolitinib: reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis. Cancer. 2020;126(6):1243-1252. doi: 10.1002/cncr.32664

2 Pettit KM, Gill H, Yacoub A, et al. A phase 2 study of the LSD1 inhibitor bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (MF): updated results and genomic analyses. Blood. 2022;140(suppl 1):9717-9720. doi.org/10.1182/blood-2022-167122

3 Gill H, Au L, Tsai D, et al. Bomedemstat (MK3543) in combination with ruxolitinib in patients with advanced myelofibrosis. Abstract #1796. Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California.