Refining Symptom Response Criteria in Polycythemia Vera Patients Treated with Ropeginterferon Alfa-2b

Background: Assessment and monitoring of disease-related symptoms is important during the treatment in polycythemia vera (PV). The original European LeukemiaNet (ELN) response criteria define a large symptom improvement as a reduction of ≥ 10 points in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). However, the LADMARK study in Korea indicated generally lower MPN-SAF TSS scores among Korean MPN patients compared to the United States patients. Additionally, a previous study suggested using changes in quartiles as potential symptomatic response thresholds (Emanuel et al., Blood 2023). Therefore, the general application of the original ELN response criteria for symptom improvement in patients with PV may be limited.

Aims: To evaluate symptom changes by MPN-SAF TSS during ropeginterferon alfa-2b treatment and to compare response rates between the original criteria and newly defined criteria for assessing large symptoms improvement.

Methods: A single-arm, open-label, phase 2 trial has been conducted to evaluate the efficacy of ropeginterferon alfa-2b in Eastern Asian patients diagnosed with PV. Symptomatic responses were measured using the validated MPN-SAF-TSS to assess changes from baseline to 12, 24, 36 and 48 weeks after ropeginterferon alfa-2b treatment. For subgroup analysis, a two-sample t-test was used to calculate p-values. The newly proposed assessment criteria for large symptoms improvement were stratified according to baseline MPN-SAF TSS: 1) baseline score <8: score remains <8, 2) baseline score 8 - <18: score decreased to ≤8, 3) baseline score 18 -<32: 5-points reduction in score, 4) baseline score ≥32: 10-points reduction in score. P-value analysis for the difference in the proportion of responders between the original ELN and Modified ELN criteria was assessed by the Chi-square test or Fisher's exact test.

Results: A total of 95 patients were evaluated in this analysis (full analysis set). The baseline mean MPN-SAF TSS was 15.93 (SD:12.58). In the subgroup analysis between hydroxyurea (HU) naïve vs Resistance or Intolerance (R/I), the baseline mean MPN-SAF TSS was higher in HU naïve group, but this was not statistically significant (HU naïve vs HU R/I: 17.71±12.79 vs 13.77±12.12 p=0.1289). When comparing low-risk to high-risk patients, there was a trend toward higher baseline MPN-SAF TSS in the high-risk group, but this was also not statistically significant (Low-risk vs High-risk: 15.65±12.33 vs 16.29±13.05 p=0.8061). Symptom burden improved after 48-weeks of treatment (mean difference in MPN-SAF TSS from baseline: -0.37±SD 12.71), with a notable improvement in concentration problems among MPN-SAF items (mean difference: -0.46 (95% CI: -0.93-0.01)). Although MPN-SAF TSS generally decreased at each assessment visit, an increase was observed particularly after 12 weeks of treatment, regardless of subgroup. When we reassessed all patients using the new assessment criteria, patients classified as symptom non-improvers by the original ENL criteria could be more precisely distinguished as either symptom improvers and non-improvers in each assessment visit.

Conclusion: Our findings suggests that while the overall symptom burden in PV patients improved after 48 weeks of ropeginterferon alfa-2b treatment, the original ELN response criteria may not adequately capture symptom improvement. The new assessment criteria allowed for a more precise evaluation of symptom changes. Further prospective studies are needed to refine these tailored symptom response criteria for PV patients, particularly those with a lower baseline symptom burden.

Yoon:Janssen, Novartis, F. Hoffmann-La Roche Ltd, Genentech, Inc.: Consultancy; Janssen: Honoraria; F. Hoffmann-La Roche Ltd, Genentech, Inc.: Research Funding.