Study Discovers Benefits of Myelofibrosis Treatment Are Not Associated With Changes in Bone Marrow

An analysis published in eJHaem found that although treatment with momelotinib and ruxolitinib improved the grade of bone marrow fibrosis in myelofibrosis patients, the improvement was not linked to an increase in overall survival (OS) or efficacy.

Furthermore, the advantage of momelotinib for anemia persisted even in the absence of improvement in bone marrow fibrosis.

Lead author Stephen Oh, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri, wrote, “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.”

Bone Marrow Fibrosis Is Not a Reliable Indicator of Response to Treatment

Data from the phase III double-blind SIMPLIFY-1 trial comparing ruxolitinib (n=160) and momelotinib (n=144) were used in the analysis. Hemoglobin levels, spleen volume, transfusion reliance, total symptom score, and bone marrow grade according to WHO guidelines were among the endpoints.

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

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

Furthermore, no correlation was found between changes in bone marrow fibrosis and either spleen (P=.126; ruxolitinib, P=.407) or symptom outcomes (P=.617; ruxolitinib, P=.833), nor between an improvement in OS and a grade increase of one or more (P=.395; ruxolitinib, P=.407).

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