Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis
Stephen T. Oh,
Srdan Verstovsek,
Vikas Gupta,
Uwe Platzbecker,
Timothy Devos,
Jean‐Jacques Kiladjian,
Donal P. McLornan,
Andrew Perkins,
Maria Laura Fox,
Mary Frances McMullin,
Adam J. Mead,
Miklos Egyed,
Jiri Mayer,
Tomasz Sacha,
Jun Kawashima,
Mei Huang,
Bryan Strouse,
Ruben Mesa
Affiliations
Stephen T. Oh
Division of Hematology Washington University School of Medicine St. Louis Missouri USA
Srdan Verstovsek
Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA
Vikas Gupta
Department of Medicine, Princess Margaret Cancer Centre University of Toronto Toronto Canada
Uwe Platzbecker
Clinic of Hematology, Cellular Therapy, and Hemostaseology University of Leipzig Medical Center Leipzig Germany
Timothy Devos
Microbiology, and Immunology, Laboratory of Molecular Immunology (Rega Institute) Department of Hematology, University Hospitals Leuven and Department of Microbiology and Immunology, Laboratory of Molecular Immunology (Rega Institute), KU Leuven Leuven Belgium
Jean‐Jacques Kiladjian
Université Paris Cité, AP‐HP, Hôpital Saint‐Louis, Centre d’Investigations Cliniques Paris France
Donal P. McLornan
Department of Haematology Guy's and St Thomas’ NHS Foundation Trust and University College Hospital London UK
Andrew Perkins
Australian Centre for Blood Diseases Monash University Melbourne Australia
Maria Laura Fox
Department of Haematology Vall d'Hebron University Hospital Barcelona Spain
Mary Frances McMullin
Centre for Medical Education Queen's University Belfast UK
Adam J. Mead
MRC Molecular Haematology Unit MRC Weatherall Institute of Molecular Medicine NIHR Biomedical Research Centre University of Oxford Oxford UK
Miklos Egyed
Department of Hematology Somogy County Kaposi Mór General Hospital Kaposvár Hungary
Jiri Mayer
Department of Internal Medicine, Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic
Tomasz Sacha
Department of Hematology Jagiellonian University Hospital Kraków Poland
Jun Kawashima
Sierra Oncology, a GSK company San Mateo California USA
Mei Huang
Sierra Oncology, a GSK company San Mateo California USA
Bryan Strouse
Sierra Oncology, a GSK company San Mateo California USA
Ruben Mesa
Atrium Health Wake Forest Baptist Comprehensive Cancer Center Wake Forest University School of Medicine Winston‐Salem North Carolina USA
Abstract Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor–naive patients from SIMPLIFY‐1 (NCT01969838), a double‐blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1‐grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.