Hydroxyurea

Current understanding

Oral cytoreductive agent, longstanding first-line cytoreduction for high-risk PV and ET. Reduces thrombosis but does not modify disease.

Evidence log

• 2026-09-29 — Rusfertide Approval Expands Options and Improves Burdens in Polycythemia Vera: cross-connection with rusfertide: Guideline inclusion of rusfertide at Category 1 for both low- and high-risk PV introduces a non-cytoreductive alternative to first-line hydroxyurea. (novelty: 4)
• 2026-08-31 — FDA Approves First-of-its-Kind Drug for Polycythemia Vera (Rusfertide/Mimrylo): cross-connection with rusfertide: Rusfertide’s FDA label targets PV patients not adequately controlled by prior cytoreductive therapies such as hydroxyurea. (novelty: 4)
• 2026-07-22 — Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance: Phase 3 RCT (trial-late) of ropeginterferon alfa-2b vs anagrelide defines the HU-resistant/intolerant ET population and further structures the post-hydroxyurea second-line decision framework in ET. (novelty: 3)
• 2026-09-01 — Genomic Evolution of Myeloproliferative Neoplasms and Therapy-Associated Mutagenesis.: Longitudinal WGS study (observational): hydroxycarbamide leaves a characteristic mutational signature in MPN blood cells, providing direct genomic evidence of drug-induced mutagenesis on top of prior clinical concerns about leukemogenic potential. (novelty: 4)
• 2025-06-26 — Efficacy and Safety of Ropeginterferon Alfa-2b in Low-Risk Polycythemia Vera.: Prospective trial-early data supporting ropeginterferon alfa-2b as a cytoreductive option in low-risk PV expands the interferon indication into a population historically managed with phlebotomy or hydroxyurea, narrowing HU’s default role when cytoreduction is needed. (novelty: 3)
• 2026-08-01 — Ropeginterferon alfa-2b in Polycythemia Vera: A systematic review and meta-analysis.: PRISMA meta-analysis of 3 RCTs (n=522, meta-analysis): ropeginterferon alfa-2b did not significantly outperform hydroxyurea on hematologic or molecular response endpoints in PV, providing pooled evidence that supports HU’s continued role as an efficacy-comparable first-line cytoreductive option despite the growing paradigm-shift narrative favoring ropeginterferon. (novelty: 3)
• 2026-08-01 — A dynamic prognostic model for polycythemia vera long-term outcomes in patients treated with ruxolitinib.: Observational (prognostic model, indirect): PV-RR6 score for ruxolitinib-treated PV formalizes 6-month response criteria (dose, spleen, phlebotomy need) analogous to ELN HU-response definitions, providing a structured way to identify ruxolitinib failures in the same high-risk PV population where HU is the alternative first-line cytoreduction. (novelty: 3)
• 2026-07-22 — Disease Burden, Inadequate Hematocrit Control, and Thromboembolic Events in Patients with Polycythemia Vera Despite Current Standard of Care Treatment: A Retrospective Claims Study.: US claims study (n=11,311, observational): hydroxyurea-treated PV patients within the broader SoC cohort continued to have inadequate HCT control (<45% not maintained in most), ongoing thromboembolic events, and substantial post-TE cost burden — real-world evidence that cytoreduction as currently delivered does not close the TE risk gap. (novelty: 3)
• 2026-07-23 — Complete Hematological Response Coupled with Molecular Response in Polycythemia Vera Treatment with Ropeginterferon Alfa-2b.: Observational series in HU-intolerant high-risk PV (n=13) demonstrates rapid CHR (~4 months) and molecular response on low-start slow-titration ropeginterferon alfa-2b, further supporting effective post-HU salvage in intolerant patients. (novelty: 3)
• 2026-07-17 — Cross-study analyses of the ropeginterferon alfa-2b effect on phlebotomy in low- and high-risk patients with polycythemia vera.: Cross-study meta-analysis documents ropeginterferon alfa-2b efficacy for phlebotomy independence and JAK2V617F allele-burden reduction in HU-resistant PV patients, further eroding hydroxyurea’s default first-line position particularly under the accelerated HIDAT regimen. (novelty: 3)
• 2026-06-04 — Selinexor Monotherapy for Cytoreduction in BCR::ABL1-Negative Myeloproliferative Neoplasms: cross-connection with selinexor-monotherapy-cytoreduction-mpn: Selinexor monotherapy is being investigated as a cytoreductive option in PV/ET/PMF, the same therapeutic niche currently dominated by hydroxyurea as first-line cytoreduction. (novelty: 4)
• 2026-06-03 — A Phase 3 Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia: Phase 3 trial (trial-late) of INCA033989 vs best available therapy in CALR-mutant ET includes prior cytoreductive therapy (typically hydroxyurea) as an enrollment criterion, framing post-HU second-line management for CALR-mutant ET. (novelty: 4)
• 2026-04-08 — A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant interferon-alpha.: Review-level synthesis (PROUD-PV/CONTINUATION-PV data) positions hydroxyurea as inferior to ropeginterferon alfa-2b for molecular remission and progression prevention in PV, supporting a paradigm shift away from HU as default first-line cytoreduction in high-risk PV. (novelty: 3)
• 2026-05-19 — TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea: Trial-early (Phase 1 open-label): hydroxyurea-resistant PV defines one of the enrolled populations in a TGR-1202 (PI3Kδ inhibitor) + ruxolitinib combination trial, extending the post-HU salvage landscape into PI3K-AKT–targeted combinations. (novelty: 3)
• 2026-03-05 — Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia: Randomized trial (trial-early): hydroxyurea serving as standard-of-care comparator arm vs pacritinib (BID, up to 48 weeks) in advanced proliferative CMML, testing whether JAK2/IRAK1/CSF1R inhibition offers superior disease control and tolerability than conventional cytoreduction in this population. (novelty: 3)
• 2026-04-23 — A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006): MK-3543-006 (Phase 3 RCT, trial-late): defines the HU-resistant/intolerant ET population randomized to bomedemstat vs best available therapy, framing post-hydroxyurea second-line management. (novelty: 3)
• 2026-04-23 — Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007): MK-3543-007 (Phase 3 RCT, trial-late): hydroxyurea serving as standard-of-care comparator arm versus bomedemstat (LSD1 inhibitor) in cytoreductive-naïve ET, testing durable clinicohematologic response. (novelty: 4)
• 2026-01-28 — A Phase 1 Study to Assess STP938 as a Monotherapy in Adults With High Risk Essential Thrombocythaemia: Defines the HU-resistant/intolerant high-risk ET population enrolled in a Phase 1 trial (trial-early) of the novel investigational agent STP938. (novelty: 4)
• 2026-04-23 — Evaluation of HU-resistance in Adult Patients With Polycythemia Vera Who Meet PV-AIM Predictors: PV-AIM real-world validation study (observational): aims to confirm baseline hemoglobin <15.5 g/dL and RDW ≥17% as predictors of hydroxyurea resistance/failure in PV, validating the machine-learning-derived PV-AIM model in clinical practice. (novelty: 3) (novelty: 3)
• 2026-03-04 — Phase IIa Study on Flonoltinib Maleate Tablets in the Treatment of Patients With Polycythemia Vera: Defines the HU-resistant/intolerant PV population enrolled in a Phase IIa trial (trial-early) of the novel JAK inhibitor flonoltinib maleate. (novelty: 4)
• 2026-03-06 — Identification of Factors Associated With Treatment Response in Patients With Polycythemia Vera, Essential Thrombocythemia, and Pre-myelofibrosis.: Observational protocol exploring whether baseline mutational profile (NGS) and cytokine signatures at diagnosis predict 12-month hematological response to hydroxyurea in PV, ET, and pre-MF — hypothesis-generating, no outcome data yet. (novelty: 3)
• 2026-03-25 — Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera: Serving as standard-of-care comparator arm in a head-to-head trial (trial-late) versus givinostat in JAK2V617F-positive high-risk PV. (novelty: 4)
• 2026-04-14 — Ropeginterferon Alfa-2b Yields Durable Responses in Essential Thrombocythemia: SURPASS-ET (Phase 3 RCT, trial-late): trial enrolled HU-intolerant or refractory ET patients, defining the post-hydroxyurea population in which ropeginterferon alfa-2b outperformed anagrelide (43% vs 6% response). (novelty: 4)
• 2026-04-28 — MITHRIDATE: Ruxolitinib Versus Hydroxycarbamide or Interferon as First Line Therapy in High Risk Polycythemia Vera: MITHRIDATE (phase III RCT, trial-late): hydroxycarbamide serving as one of two standard-of-care comparator arms versus ruxolitinib in first-line high-risk PV. (novelty: 4)

Open questions

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