Abstract
In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.
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Funding
Low-PV is sponsored by FROM, Fondazione per la Ricerca Ospedale di Bergamo ETS and endorsed by the AIRC–Gruppo Italiano Malattie Mieloproliferative (AGIMM) with the program number 1005 and MYNERVA project with program number 21267, website at https://progettomynerva.it. Drug supply (Ropeginterferon alfa-2b) and financial support were provided by AOP Health (Vienna, Austria).
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TB conceived and designed the study, supervised the analysis, and wrote the paper. AC performed statistical analysis and contributed to manuscript writing. FF was in charge of project and data management. AG and GC critically revised the data analysis. AMV revised the study and contributed to manuscript writing. LC and FG were in charge of the management of samples for the biological subproject. AAL collected and analyzed data for the validation set from the Spanish registry. VDS, ERo, FC, MBo, AI, FPal, GB, FPan, ARi, GC, MC, DR, CM, SS, ERu, AP, NC, BM, EC, GGL, PG, SB, FR, FL, LS, CB, DC, NV, MBe, MCF, GT, and ARa collected data. All authors revised and approved the final version of the manuscript.
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Barbui, T., Carobbio, A., De Stefano, V. et al. Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes. Ann Hematol 103, 437–442 (2024). https://doi.org/10.1007/s00277-023-05577-9
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DOI: https://doi.org/10.1007/s00277-023-05577-9