Sistema de Salut de Catalunya
Institut Català de la Salut
[Oh ST] Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA. [Verstovsek S] Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [Gupta V] Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. [Platzbecker U] Clinic of Hematology, Cellular Therapy, and Hemostaseology, University of Leipzig Medical Center, Leipzig, Germany. [Devos T] 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. [Kiladjian JJ] Université Paris Cité, AP-HP, Hopital Saint-Louis, Centre d’Investigations Cliniques, Paris, France. [Fox ML] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-03-04T14:12:08Z
2024-03-04T14:12:08Z
2024-02-05
JAK inhibitor; Bone marrow fibrosis; Momelotinib
Inhibidor de JAK; Fibrosi de la medul·la òssia; Momelotinib
Inhibidor de JAK; Fibrosis de la médula ósea; Momelotinib
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.
This study was sponsored by Sierra Oncology, a GSK company.
Article
Published version
English
Mielofibrosi - Tractament; Proteïnes quinases - Inhibidors - Ús terapèutic; DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Primary Myelofibrosis; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors::Janus Kinase Inhibitors; ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::mielofibrosis primaria; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas::inhibidores de las cinasas Janus
Wiley
eJHaem;5(1)
https://doi.org/10.1002/jha2.854
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3437]
