Early Phase II Results Support Safety and Efficacy of Bomedemstat in Combination with Ruxolitinib in Patients with Myelofibrosis

Early results of a phase II study suggest that the addition of bomedemstat to a ruxolitinib regimen is well tolerated, improves splenomegaly and symptom scores, and stabilizes hemoglobin both in the frontline and second-line setting in patients with myelofibrosis (MF), according to a presentation at the 65th American Society of Hematology Annual Meeting and Exposition by Harinder Gill, MD, MBBS, FRCP, FRCPath, of the University of Hong Kong, and colleagues.

Bomedemstat is an oral lysine-specific demethylase-1 (LSD1) inhibitor clinically active in patients with myeloproliferative neoplasms (MPNs) and has shown clinical activity as a single agent in patients with MF, according to the researchers. LSD1 is a histone demethylase critical for self-renewal of malignant hematopoietic stem cells and for maturation of progenitor cells.

The ongoing, open-label, phase II study is investigating the combination of bomedemstat and ruxolitinib in treatment-naïve patients with MF or those with a suboptimal response to ruxolitinib, with the objectives of evaluating the safety and tolerability of the combination, the optimal dosing of bomedemstat in this regimen, and the efficacy of the combination as assessed by spleen size reduction and symptom reduction using the Myelofibrosis Symptom Assessment Form (MFSAF).

The median duration of ruxolitinib plus bomedemstat was 12 weeks. In 20 evaluable patients at week 12, 12 patients (60%) had stable (∆ <±1.0 g/dL) or improved hemoglobin (>1.0 g/dL), five patients (25%) had ≥50% reduction in MFSAF Total Symptom Score, and 18 patients (65%) had ≥30% spleen length reduction. In six patients evaluable for molecular responses by droplet digital polymerase chain reaction at week 12, four patients (67%) had reductions in JAK2^V617F allele frequencies, with one patient (17%) having ≥50% reduction.

The most common nonhematologic adverse events were diarrhea, malaise, edema, and dysgeusia, all grade 1 or 2. There were no safety signals, dose-limiting toxicities, or deaths related to treatment.

Reference

Gill H, Au L, Leung GMK, et al. Phase 2 study to assess the safety and efficacy of bomedemstat (MK3543) in combination with ruxolitinib in patients with myelofibrosis. Abstract #621. Presented at the 65th American Society of Hematology Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.