Methodological challenges in the development of endpoints for myelofibrosis clinical trials.

Autor:	Barosi G; Center for the Study of Myelofibrosis, IRCCS Policlinico S Matteo Foundation, Pavia, Italy. Electronic address: barosig@smatteo.pv.it., Tefferi A; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA., Gangat N; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA., Szuber N; University of Montreal, Montreal, QC, Canada., Rambaldi A; Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy., Odenike O; Leukemia Program, University of Chicago Medicine and University of Chicago Comprehensive Cancer Center, Chicago, IL, USA., Kröger N; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Gagelmann N; Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Talpaz M; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gale RP; Centre for Haematology, Department of Immunology and Inflammation, Imperial College of Science, Technology and Medicine, London, UK.
Jazyk:	angličtina
Zdroj:	The Lancet. Haematology [Lancet Haematol] 2024 May; Vol. 11 (5), pp. e383-e389. Date of Electronic Publication: 2024 Apr 08.
DOI:	10.1016/S2352-3026(24)00067-X
Abstrakt:	Myelofibrosis is a myeloid neoplasm characterised by the presence of JAK2, CALR, or MPL mutations (with a 90% mutation frequency) and trilineage myeloid proliferation with prominent megakaryocyte atypia. People with myelofibrosis have a lower survival rate and poorer quality of life than healthy individuals. Therapy for myelofibrosis uses Janus kinase inhibitors, which reduce splenomegaly and alleviate symptoms. Regulatory approvals for Janus kinase inhibitors have focused on this dual endpoint. In this Viewpoint, we discuss the validity of using spleen reduction as a surrogate endpoint for the disease-modifying activity of candidate drugs for myelofibrosis. We suggest alternative endpoints addressing unmet patient needs, including progression-free survival and overall survival. Moreover, we highlight the importance of selecting a core set of crucial outcomes with which we can individualise clinical decision making and standardise reporting of clinical trials results. We propose selecting patient-reported outcomes and anaemia response. We also suggest integrating economic considerations in the process of evaluating new drugs for myelofibrosis. Competing Interests: Declaration of interests NGan has received honoraria for an educational event from OncoLive. AR has received honoraria for lectures or presentations from Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros; has received support for attending meetings or travel from Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros; and has participated on a data safety monitoring board or advisory board for Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros. OO has received consulting fees from Servier, Rigel, AbbVie, Incyte; and has received fees from Threadwell Therapeutics for their service on a data safety monitoring board for an ongoing clinical trial. NK has received honoraria for lectures from Kite–Gilead, Jazz, MSD, Neovii Biotech, Alexion, MSD, Taked, Novartis, Riemser, Pfizer, and BMS; and has received research support from Neovii, Riemser, Novartis, and DKMS. NGag has received consulting fees from MorphoSys and Stemline. MT has received consulting or advisory fees from Novartis, Bristol Myers Squibb–Celgene, Kyowa Kirin International, Imago Pharma, SDP Oncology, Sierra Oncology, and GlaxoSmithKline; and has received research funding from Bristol Myers Squibb–Celgene and Arcus Biosciences. HK has received honoraria for participation on an advisory board and consulting from AbbVie, Amgen, Ascentage, Amphista, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Labcorp, Novartis, Pfizer, Shenzhen Target Rx, Stemline, Takeda; and has received research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi Sankyo, Immunogen, Jazz, and Novartis. RPG is a consultant for Antengene; Medical Director of FFF Enterprises; a speaker for Janssen Pharma and Hengrui Pharma; on the board of directors for the Russian Foundation for Cancer Research Support; and on the scientific advisory board for StemRad. All other authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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