Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

SIMPLE SUMMARY: The prognostic relevance of a patient achieving complete response to hydroxyurea, the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. A retrospective, real-world analysis was performed on 563 polycythemia vera patients treated with hydroxyurea for ≥12 months during an observational “PV-NET” Italian study. We investigated factors associated with a complete response to hydroxyurea and outcomes of the 397 poor responders to hydroxyurea according to whether they subsequently received ruxolitinib (n = 114) or continued hydroxyurea (n = 283). The results suggest that many PV patients receive underdosed hydroxyurea, leading to lower response and toxicity rates. In addition, many patients continued hydroxyurea despite a poor clinical or hematological response; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised. ABSTRACT: In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients’ triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised.