Introduction As recommended by NCCN Guidelines, Ropeginterferon Alfa-2b (Ropeg) is a therapy of choice for both low and high-risk Polycythemia Vera (PV) patients. It has a favourable dosing schedule and offers clinically advantageous hematologic and molecular responses, with potential disease modifying activity. However, the evidence of its longitudinal response and real-world evidence of its long-term use is lacking.

Methods This observational real-world study included patients diagnosed with PV and treated with Ropeg at nine hematology centers across Italy. Baseline data, prior treatments, dosing and subsequent hematologic responses were documented at 3, 6, 9, 12, 18, and 24 months. Discontinuation rates and reasons were also recorded. A logistic regression model was used to evaluate the association between early dose escalation, treatment duration, and median dose with the likelihood of achieving complete hematologic response (CHR). The analysis was conducted on a longitudinal dataset, including repeated observations for each patient.

Results Among the 133 patients analyzed (median age 53.4 years, range 19-85; 69.9% male), most (78.2%, n=104) had previously been treated with hydroxyurea; of these, two had also received ruxolitinib. The median duration of prior cytoreductive therapy was 18.2 months (range, 0.2–229.2), with the main reason for discontinuation being intolerance (71.2%), followed by suboptimal efficacy (25%) and reproductive concerns (3.8%). Ropeg was used as a first-line treatment in 29 patients. The initial median dose of Ropeg was 100 mcg (range, 50–100 mcg). During a median Ropeg exposure of 11.5 months (range, 1–41 months), clinical and hematologic responses consistently improved over time. The rate of CHR nearly doubled, from 28.7% at 3 months to 56.5% at 24 months. Hematocrit control improved from 55.8% to 75%, likewise the need for therapeutic phlebotomy decreased from 33.6% to 20%. WBC normalization was achieved in 81.4% at 3 months and reached 100% by 24 months. Similarly, platelet response increased from 53.1% to 85% over the same time period.

The logistic regression model revealed that patients who experienced an early increase in dose had significantly higher odds of achieving a response (β = 0.91, p < 0.001). Additionally, extended treatment duration was positively linked to CHR rates (β = 0.36, p = 0.011). Interestingly, these two factors interacted significantly (β = 0.59, p < 0.001), suggesting that those who experienced early dose escalation benefited more from longer treatment. Conversely, a higher median dose was associated with a decreased likelihood of response (β = -0.006, p < 0.001). The overall model fit was satisfactory (AIC = 1952.6).

Discontinuation occurred in 20 patients (15%) due to adverse events (8.2%), lack of response (5.2%) (specifically, 3 patients for unresolved itching) and patient preference (1.4%), after a median treatment duration of 6.8 months (range: 0.5–17).

Conclusion This study supports the clinical utility of Ropeg in the treatment of PV, highlighting that both early dose escalation and extended treatment duration are linked to improved hematologic outcomes. The lack of association between higher dose and CHR may reflect underlying biological among patients who require higher doses. While further studies are needed to assess long-term efficacy, these findings offer practical insights for optimizing dosing strategies in clinical practice. Additionally, recent evidence suggests that starting with a higher dose and implementing a more rapid titration schedule (e.g., 250-350-500 mcg) may result in faster hematologic remission, with CHR rates at six months comparable to those typically seen at twelve months using conventional low-dose, slow-escalation regimens. Though direct comparisons are lacking, these data point to the potential value of more proactive, individualized dose adjustments.

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2025
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