The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF)

British Journal of Haematology - Tập 176 Số 1 - Trang 76-85 - 2017
Ruben A. Mesa1, Alessandro M. Vannucchi2, Abdulraheem Yacoub3, Pierre Zachée4, Mamta Garg5, Roger M. Lyons6, Steffen Koschmieder7, Ciro R. Rinaldi8, Jenny Byrne9, Yasmin Hasan10, Francesco Passamonti11, Srđan Verstovšek12, Deborah Hunter13, Mark M. Jones13, Hui‐Ling Zhen13, Dany Habr14, Bruno Martino15
1Mayo Clinic Cancer Center, Scottsdale, AZ, USA
2Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy
3University of Kansas Medical Center, Westwood, KS, USA
4ZNA Stuivenberg, Antwerp, Belgium
5Leicester Royal Infirmary, Leicester, UK;
6Texas Oncology and US Oncology Research, San Antonio, TX, USA
7Department of Haematology, Oncology, Haemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
8University of Lincoln and United Lincolnshire Hospital Trust, Lincoln, UK
9Nottingham University Hospitals, Nottingham, UK
10Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, UK
11University of Insubria, Varese, Italy
12University of Texas/MD Anderson Cancer Center, Houston, TX USA
13Incyte Corporation, Wilmington, DE, USA.
14Novartis Pharmaceuticals, East Hanover, NJ, USA
15Azienda Ospedaliera “Bianchi Melacrino Morelli”, Reggio Calabria, Italy

Tóm tắt

SummaryThe randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.

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British Journal of Haematology

Tập 176 Số 1

76-85

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