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)

Abstract

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.

JAK2 inhibitors for myeloproliferative neoplasms: what is next?

“…28 However, in the phase 3b RELIEF trial, which evaluated switching to ruxolitinib in patients with PV and persistent symptoms despite good hematocrit control on a stable dose of HU, this strategy was not statistically significantly superior to continuing on HU, as assessed by the rate of $50% reduction in the TSS cytokine symptom cluster (the sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at week 16. 141 Several trials are currently evaluating ruxolitinib in high risk-ET (NCT02962388, NCT02577926). Specifically, strategies aimed at regulatory approval in both the United States and Europe are focusing on a second-line indication in patients resistant to or intolerant of HU, 142 comparing the drug with anagrelide or interferon alfa (eg, NCT03123588, NCT02962388).…”

Developmental Therapeutics in Myeloproliferative Neoplasms

“…33 Patients were randomized 1:1 to switch to ruxolitinib (n = 54) or stay on HU (n = 56), with crossover to ruxolitinib permitted after week 16. This trial missed its primary endpoint, a ≥ 50% improvement from baseline in the MPN-SAF TSS cytokine symptom cluster (the sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at week 16, although this was achieved by more patients in the ruxolitinib than in the HU continuation group (43.4% versus 29.6%, p = 0.139).…”

Management of symptoms in polycythemia vera and essential thrombocythemia patients

“…A variation of this tool (MPN-SAF TSS Cytokine) was used in the RELIEF study evaluating ruxolitinib in PV. 23 The MPN-10 has been recommended by the International working group (IWG) for use in clinical trials. 24 Table 1 illustrates the development of the MPN PRO tools and the symptom components assessed.…”