Study Finds Bone Marrow Changes Not Linked With Myelofibrosis Treatment Benefits

While treatment with momelotinib and ruxolitinib improved bone marrow fibrosis grade in patients with myelofibrosis, the improvement was not associated with increased overall survival (OS) or efficacy, according to an analysis presented in eJHaem.

Additionally, the benefit to anemia with momelotinib was present regardless of bone marrow fibrosis improvement.

“These data suggest that the anemia benefit of momelotinib is not linked to [bone marrow fibrosis] changes and question the use of [bone marrow fibrosis] assessment as a surrogate marker for clinical benefit with [Janus kinase] inhibitors,” wrote lead author, Stephen Oh, MD, PhD, at Washington University School of Medicine in St. Louis, Missouri.

Bone Marrow Fibrosis Not Effective Marker for Treatment Response

The analysis utilized data from the phase III double-blind SIMPLIFY-1 trial on momelotinib (n=144) versus ruxolitinib (n=160). Endpoints included bone marrow grade per World Health Organization criteria, Total Symptom Score, spleen volume, transfusion dependency, and hemoglobin levels.

In patients with increases of one or more in bone marrow fibrosis grade, 87% of those on momelotinib achieved transfusion independence versus 44% on ruxolitinib. In patients with stable or worsening grade, 76% and 56% of those on momelotinib and ruxolitinib achieved transfusion independence, respectively.

Notably, bone marrow fibrosis grade changes were not associated with transfusion independence for momelotinib (P=.350) or ruxolitinib (P=.096), and hemoglobin levels generally increased with momelotinib but decreased with ruxolitinib, regardless of grade changes.

Additionally, changes in bone marrow fibrosis were not associated with spleen (momelotinib, P=.126; ruxolitinib, P=.407) or symptom outcomes (momelotinib, P=.617; ruxolitinib, P=.833), nor was a grade increase of one or more associated with improved OS (momelotinib, P=.395; ruxolitinib, P=.407).

“The clinical significance of [bone marrow fibrosis] changes with nontransplant therapies for myelofibrosis should be carefully evaluated to better understand its role in disease modification, the pathogenesis of myelofibrosis, and clinically important outcomes,” wrote Dr. Oh and colleagues.

Related: Can Splenic Irradiation Improve HSCT for Myelofibrosis?

Reference

Oh ST, Verstovsek S, Gupta V, et al. Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis. EJHaem. 2024;5(1):105-116. Published 2024 Feb 5. doi:10.1002/jha2.854