J Korean Med Sci.  2024 Jan;39(3):e24. 10.3346/jkms.2024.39.e24.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients

• Lee SE
• Hong J
• Bang SM
• Park J
• Choi CW
• Bae SH
• Kim MK
• Yoon SY
• Kim SY

• KMID: 2551176
• DOI: http://doi.org/10.3346/jkms.2024.39.e24

Abstract

Background
Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients.
Methods
The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I.
Results
The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83–21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival.
Conclusion
These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Keyword

Polycythemia Vera; Hydroxyurea; Drug Resistance; Intolerance

Figure

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  Fig. 1 Cumulative incidence of thrombosis (A) and disease progression (B) of polycythemia vera patients after developing HU-R or HU-I.HU-R = hydroxyurea-resistance, HU-I = hydroxyurea-intolerance.

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  Fig. 2 Progression-free survival (A) and overall survival (B) of polycythemia vera patients after developing HU-R or HU-I.HU-R = hydroxyurea-resistance, HU-I = hydroxyurea-intolerance.

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