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)

Mesa, Ruben; Byrne, Jenny; Vannucchi, Alessandro M.; Yacoub, Abdulraheem; Zachee, Pierre; Garg, Mamta; Lyons, Roger; Koschmieder, Steffen; Rinaldi, Ciro; Hasan, Yasmin; Passamonti, Francesco; Verstovsek, Srdan; Hunter, Deborah; Jones, Mark M.; Zhen, Huiling; Habr, Dany; Martino, Bruno

Abstract

The 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.

Citation

Mesa, R., Byrne, J., Vannucchi, A. M., Yacoub, A., Zachee, P., Garg, M., …Martino, B. (2017). 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, 176(1), 76-85. https://doi.org/10.1111/bjh.14382

• Journal Article Type: Article
• Acceptance Date: Aug 11, 2016
• Online Publication Date: Nov 8, 2016
• Publication Date: Jan 1, 2017
• Deposit Date: Jan 31, 2018
• Publicly Available Date: Jul 31, 2019
• Journal: British Journal of Haematology
• Print ISSN: 0007-1048
• Electronic ISSN: 1365-2141
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 176
• Issue: 1
• Pages: 76-85
• DOI: https://doi.org/10.1111/bjh.14382
• Public URL: https://nottingham-repository.worktribe.com/output/1119615
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.14382
• PMID: 27858987