Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission

Polycythaemia vera is driven by a single recurrent mutation in almost every patient, yet no treatment is given with the aim of eliminating it. Ropeginterferon alfa-2b lowers the JAK2 V617F allele burden year on year in PROUD-PV and CONTINUATION-PV, and a fraction of patients reach very low burdens. Ruxolitinib blocks wild-type and mutant JAK2 alike, which limits its dose and spares the clone. Mutant-selective JAK2 V617F inhibitors are now in first-in-human trials. The idea is to test interferon plus a mutant-selective inhibitor against interferon alone with molecular response and progression, not haematocrit, as the endpoints.