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Optimizing Hydroxyurea Management Among Patients With Polycythemia Vera

Amber Denham

Results of a retrospective, real-world analysis determined that many patients with chronic myeloproliferative neoplasm (MPN) polycythemia vera (PV) received underdosed hydroxyurea, which led to lower complete response and toxicity rates, as well as proceeded with hydroxyurea regardless of poor clinical or hematological responses. These results highlight the need for more optimized hydroxyurea management and intervention in less-than-optimal responders. 

“Hydroxyurea is currently the most used cytoreductive therapy for PV patients at high risk of thrombosis, with most patients achieving adequate control of the disease with acceptable tolerance,” Francesca Palandri, MD, Universitaria di Bologna, Bologna, Italy, and coauthors explained. “However, many patients may only obtain a poor response to [hydroxyurea] or develop drug-related toxicities during therapy.”

This study sought to define clinical characteristics associated with the achievement of complete response (CR) to hydroxyurea, investigate whether the type of suboptimal response may influence a decision to switch to ruxolitinib, and assess if a patient achieving CR to hydroxyurea would improve outcome parameters. The analysis included 563 patients with polycythemia vera treated with hydroxyurea for ≥12 months during an observational “PV-NET” Italian study. Among this patient population, 166 patients achieved complete response (CR), 264 achieved partial response (PR), and 133 achieved no response (NR). 

In a multivariate analysis, the absence of splenomegaly (P = 0.03), pruritus (P = 0.002), and a median hydroxyurea dose of ≥1 g/day (P < 0.001) remained associated with CR. Overall, 283 patients who received either CR or PR continued hydroxyurea, and 114 patients switched to ruxolitinib. It was noted that many patients continued hydroxyurea despite a PR/NR and that splenomegaly and other symptoms were the main drivers of an early switch.

A median hydroxyurea dose of ≥1 g/day was correlated with more frequent adverse events. In the 449 patients who were receiving only hydroxyurea, rates of thrombosis, hemorrhages, progression, and overall survival (OS) were comparable among the CR, PR, and NR groups.

Palandri et al concluded, “Better [hydroxyurea] management, standardization of the criteria for and timing of responses to [hydroxyurea], and adequate intervention in poor responders should be advised.”


Source:

Palandri F, Rossi E, Auteri G, et al. Predictors of response to hydroxyurea and switch to ruxolitinib in HU-resistant polycythemia VERA patients: A real-world PV-NET study. Cancers. Published online July 21, 2023. doi:10.3390/cancers15143706