Evaluating the feasibility of a network meta-analysis comparing treatment options in polycythemia vera

Aim: Polycythemia vera (PV), a rare, chronic myeloproliferative neoplasm, that negatively impacts patient outcomes, and optimal therapy remains unclear due to a lack of head-to-head trials. A targeted literature review and feasibility assessment for an indirect comparison of ropeginterferon alfa-2b-njft versus peginterferon alfa-2a or ruxolitinib, using standard of care comprising hydroxyurea (HU) as a common comparator was conducted. Materials & methods: A targeted literature review evaluated clinical comparative evidence for PV treatments published between January 2014 and May 2024 in PubMed and relevant conference abstracts. End points of interest included complete hematologic response, molecular response, allele burden, event-free survival and safety. The feasibility of a network meta-analysis (NMA) was evaluated based on homogeneity of patient populations, treatment regimens and end point definitions. Results: Of 193 PubMed records and 460 conference abstracts screened, 40 records were included, representing evidence from 11 randomized controlled trials and 10 observational studies. Among these, 20 studies formed connected evidence networks for the end points of interest. Substantial heterogeneity across studies precluded a robust NMA: patient populations varied (newly diagnosed, high-risk, low-risk, HU-refractory or -intolerant), complete hematologic response definitions differed (e.g., requirement for absence of disease-related symptoms), molecular response thresholds were inconsistent, follow-up durations varied and definitions of standard of care ranged from almost exclusive use of HU to mixed regimens. Conclusion: An NMA for PV treatments was not feasible due to significant clinical and methodological heterogeneity across studies, including differences in patient characteristics, treatments, outcome definitions and follow-up times. These findings highlight the importance of standardized clinical trial designs and outcome definitions to enable robust comparative evidence generation for rare conditions like PV.