Ropeginterferon-α2b discontinuation after long-term exposure: four cases from a single institution.

Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm driven by JAK2 mutations, leading to the overproduction of blood cells. Ropeginterferon-α-2b (RopegIFN) has emerged as a promising therapy, capable of lowering the JAK2V617F allele burden and maintaining a complete hematologic response (CHR). Here, we report the cases of four patients with PV who discontinued RopegIFN after achieving CHR. One patient had sustained long-term remission post-discontinuation, with the JAK2V617F allele burden reduced below 10%, and met the criteria for an "operational cure." However, the other three patients experienced rising blood counts, resulting in loss of CHR. These findings underscore the importance of a robust molecular response in predicting sustainable remission. Continuous therapy remains the standard approach due to the lack of predictive models to identify patients who can safely discontinue RopegIFN. In the future, it will be necessary to verify whether patients who have achieved an "operational cure" can remain treatment free.