Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

Autor:	Harrison CN; Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Nangalia J; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.; Wellcome Sanger Institute Hinxton, Cambridgeshire, United Kingdom.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Boucher R; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom., Jackson A; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom., Yap C; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom.; Clinical Trials and Statistics Unit, The Institute of Cancer Research, United Kingdom., O'Sullivan J; Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.; Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, NIHR, Biomedical Research Centre, University of Oxford, Oxford, United Kingdom., Fox S; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom., Ailts I; Department of Internal Medicine, Mayo Clinic, Phoenix, AZ., Dueck AC; Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ., Geyer HL; Department of Internal Medicine, Mayo Clinic, Phoenix, AZ., Mesa RA; Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, TX., Dunn WG; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Nadezhdin E; Wellcome Sanger Institute Hinxton, Cambridgeshire, United Kingdom., Curto-Garcia N; Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Green A; Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Wilkins B; Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Coppell J; Royal Devon & Exeter NHS Foundation Trust, Exeter, United Kingdom., Laurie J; Worthing Hospital, Western Sussex NHS Foundation Trust, Worthing, United Kingdom., Garg M; University Hospital of Leicester, Leicester, United Kingdom., Ewing J; Birmingham Heart of England NHS Foundation Trust, Birmingham, United Kingdom., Knapper S; School of Medicine, Cardiff University, Cardiff, United Kingdom., Crowe J; Royal United Hospital Bath NHS Trust, Bath, United Kingdom., Chen F; Queen Elizabeth Hospital, Birmingham, United Kingdom., Koutsavlis I; Western General Hospital, Lothian Health Board, Edinburgh, United Kingdom., Godfrey A; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Arami S; London North West Healthcare NHS Trust, London, United Kingdom., Drummond M; The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom., Byrne J; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom., Clark F; Queen Elizabeth Hospital, Birmingham, United Kingdom., Mead-Harvey C; Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ., Baxter EJ; Haematology, Cambridge Blood and Stem Cell Biobank NHS-BT Cambridge Centre, Cambridge, United Kingdom., McMullin MF; Queen's University, Belfast, United Kingdom., Mead AJ; Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, NIHR, Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.; Cancer and Haematology Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Jul 01; Vol. 41 (19), pp. 3534-3544. Date of Electronic Publication: 2023 May 01.
DOI:	10.1200/JCO.22.01935
Abstrakt:	Purpose: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. Patients and Methods: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. Results: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2 V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2 V617F stem/progenitor cells. ASXL 1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. Conclusion: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
Databáze:	MEDLINE
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