SP28 | SAFE AND EFFECTIVE COMBINATION OF ROPEG-INTERFERON α-2B AND RUXOLITINIB IN REFRACTORY POLYCYTHEMIA VERA: A CASE REPORT

Background. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with thrombotic risk and potential evolution to myelofibrosis or acute leukemia. Treatment is risk-adapted (based on age and vascular events), with a conservative approach in low-risk patients and cytoreductive drugs reserved for high-risk PV. Novel agents (e.g., ropeg-interferon α-2b, Ropeg, and ruxolitinib, RUX) and their combination (CT) may offer an option for more aggressive disease. Case description. A 42-year-old male was diagnosed with low-risk PV in 2016, initially treated with antiplatelet therapy alone. Due to high phlebotomy need and splenomegaly, hydroxyurea (HU) was introduced. In 2022, portal vein thrombosis up-stratified PV to high-risk. In January 2023, for suboptimal hematologic control and persistent splenomegaly, treatment switched to Ropeg, achieving partial response. After one year, due to splenomegaly progression, RUX was started as third-line therapy with limited hematologic improvement and spleen decrease. After off-label authorization, CT with RUX and Ropeg was initiated. After six months, the patient achieved complete hematologic response, requiring only one phlebotomy, with relevant spleen volume reduction (15.5 vs. 19 cm) and decreased JAK2 V617F allelic burden (18.94% vs. 44.72%). Discussion To our knowledge, this is the first reported case of combining RUX and Ropeg for refractory PV. In the literature, the phase 2 COMBI I trial demonstrated the safety and efficacy of RUX and pegylated interferon α-2a in patients resistant to interferon and HU. Our case supports the safe use of RUX-Ropeg combination, achieving hematologic response and spleen reduction. This clinical benefit may reflect the synergistic mechanisms of action between the two agents, with RUX anti-inflammatory effects potentially enhancing Ropeg activity. The observed molecular response, with marked JAK2 V617F burden reduction, suggests selective targeting of the malignant clone and may translate into improved outcomes, as previously shown in the CONTINUATION-PV and MAJIC-PV studies. Conclusion. This case supports the safety and efficacy of combining RUX and Ropeg as an intensified approach in selected refractory PV patients. Further studies are warranted to assess long-term outcomes, including potential bone marrow improvement suggesting a disease-modifying effect. Moreover, future research could help to identify patients who may benefit from early CT as first-line treatment.