2026-04-17T01:08:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/111542025-10-24T10:35:00Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Oh, Stephen author Verstovsek, MD, PhD, Professor of Medicine, Srdan author Gupta, Vikas author Platzbecker, Uwe author Devos, Timothy author Kiladjian, Jean-Jacques author Fox, Maria Laura author 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. http://hdl.handle.net/11351/11154 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 Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis