Identification of Factors Associated With Treatment Response in Patients With Polycythemia Vera, Essential Thrombocythemia, and Pre-myelofibrosis.
Key claim: Biological factors at diagnosis — specifically mutational profile by NGS and cytokine profile — may predict hematological response to hydroxyurea or pegylated interferon at 12 months in patients with PV, ET, and pre-myelofibrosis.
Abstract
First-line treatment for patients with polycythemia vera, essential thrombocythemia, and pre-myelofibrosis is based on hydroxyurea or pegylated interferon. The objective of treatment is to prevent thrombotic complications and leukemic transformation. Despite overall good response rates, some patients do not respond to treatment and others lose their response over time. Both situations are associated with worse survival and there are to date no clear predictive factors for response although the existence of additional mutations seems unfavorable.
In this exploratory study, we hypothesize that biological factors at diagnosis are associated with hematological response at 12 months. We will more specifically study the association between mutational profile, assessed by next-generation sequencing, and cytokine profile with hematological response.
This study will help in identifying patients who will not respond to hydroxyurea or pegylated interferon and give the opportunity to try other treatments upfront, in the perspective of precision medicine. On the basic science side, this study will help in understanding the molecular and immunological factors involved in resistance to treatment.
Why this matters
Frontline cytoreduction in PV, ET, and pre-PMF currently relies on age/thrombosis-based risk rather than disease biology, leaving choice between hydroxyurea and pegylated interferon largely empirical. Linking diagnostic NGS mutational profiles and cytokine signatures to 12-month hematological response could yield subtype-specific predictors that refine natural history models and enable biology-driven treatment assignment across these chronic-phase MPNs.