Momelotinib long-term safety and survival in myelofibrosis : integrated analysis of phase 3 randomized controlled trials
Verstovsek, Srdan (The University of Texas, USA)
Mesa, Ruben (University of Texas Health Science Center at San Antonio)
Gupta, Vikas (Princess Margaret Cancer Centre (Toronto, Canadà))
Lavie, David (Hadassah-Hebrew University Medical Center, Jerusalem, Israel)
Dubruille, Viviane (Centre Hospitalier Universitaire de Nantes)
Cambier, Nathalie (Centre Hospitalier Régional Universitaire de Lille)
Platzbecker, Uwe (University of Leipzig, Germany)
Hus, Marek (Uniwersytet Medyczny w Lublinie, Lublin, Poland)
Xicoy, Blanca (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Oh, Stephen T. (Washington University School of Medicine, St. Louis, USA)
Kiladjian, Jean Jacques (Universite de Paris, France)
Vannucchi, Alessandro M. (Careggi University Hospital (Florència, Itàlia))
Gerds, Aaron (Cleveland Clinic, USA)
Egyed, Miklos (Teaching Hospital Mor Kaposi, Kaposv ' ar, Hungary)
Mayer, Jiří (Masaryk University, Brno, Czech Republic)
Sacha, Tomasz (Uniwersytet Jagiellonski Collegium Medicum, Krakow, Poland)
Kawashima, Jun (Sierra Oncology, San Mateo, CA)
Morris, Marc (Sierra Oncology, San Mateo, CA)
Huang, Mei (Sierra Oncology, San Mateo, CA)
Harrison, Claire (National Health Services (NHS) Foundation Trust, London, United Kingdom)

Data:	2023
Resum:	Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for ≥5 years, with a median treatment exposure of 11. 3 months (range, 0. 1-90. 4 months). The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Blood advances, Vol. 7 Núm. 14 (july 2023) , p. 3582-3591, ISSN 2473-9537

DOI: 10.1182/bloodadvances.2022009311
PMID: 37042865

10 p, 345.6 KB

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