Interferon Lowers Myelofibrosis Risk in Young Patients With Polycythemia Vera, Essential Thrombocytopenia

Early treatment with interferon reduced secondary myelofibrosis (sMF) risk in adolescent and young adult (AYA) patients with polycythemia vera (PV) or essential thrombocytopenia (ET), according to study data published in Leukemia.¹

Red blood cells | Image Credit: © fotogurmespb - stock.adobe.com

MF is an incurable, rare hematologic malignancy characterized by the overproduction of red blood cells. This causes bone marrow scarring, which leads to severe anemia—a key factor impacting overall survival (OS) for patients with MF. It can develop as a primary disease or secondary to ET and PV, as well as progress to acute myeloid leukemia in some cases. Although MF is primarily diagnosed in older adults, 20% of cases are in individuals under the age of 40.^1,2

AYA patients with ET or PV face unique clinical challenges due to their longer life expectancy because of a lack of data on long-term outcomes and treatment strategies. Existing guidelines are specific to older populations, despite the unique clinical considerations in younger patients.¹

“These patients are expected to live for several decades, and the accumulation of additional thrombotic risk factors (age, cardiovascular conditions, additional mutations) may progressively heighten this risk,” the authors wrote. “This highlights a substantial and emerging concern regarding thrombotic events in this younger demographic.”¹

The study evaluates complication rates, including thrombosis and progression to sMF, and the impact of interferon (IFN) on outcomes in patients diagnosed before the age of 25. The primary outcomes of the study were thrombosis-free survival (TFS), myelofibrosis-free survival (MFS), and OS in the entire cohort and for ET and PV patients separately, and the impact of treatment on these outcomes. Secondary outcomes were identification of risk factors associated with thrombotic events and sMF.¹

The study included a total of 348 patients, of whom 278 were diagnosed with ET and 70 with PV, with a median age at diagnosis of 20 years. The incidence of thrombotic events was about 1.9 per 100 patient-years, with elevated white blood cell count (≥ 11 × 10⁹/L) and absence of splenomegaly at diagnosis identified as significant risk factors. However, cytoreductive therapy did not reduce thrombotic risk. The incidence of sMF was 0.7 per 100 patient-years, with CALR mutations and a history of thrombosis associated with higher risk.¹

Whereas hydroxyurea and other cytoreductive agents are frequently used in older patients, interferon offers a distinct mechanism of action and has been associated with disease-modifying effects, including allele burden reduction. In this study, first-line treatment with interferon significantly improved MFS compared to other therapies or no cytoreductive treatment. These findings support a potential shift in clinical practice for younger patients with ET or PV, highlighting interferon as a promising option for long-term disease control and risk reduction.¹

“Crucially, the high risk of disease progression in this population highlights the need for therapies that can address this risk,” the authors concluded. “Notably, no progression was observed in AYA patients treated with INF, strongly supporting its potential as a first-line treatment for this younger group, who are expected to live with their [myeloproliferative neoplasm] for many years.”¹

REFERENCES

1. Beauverd Y, Ianotto JC, Thaw K.H, et al. Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera. Leukemia. May 12, 2025. Doi:10.1038/s41375-025-02545-2

2. Ruxolitinib discontinuation at conditioning does not increase GVHD risk in myelofibrosis. Pharmacy Times. May 7, 2025. Accessed May 15, 2025. https://www.pharmacytimes.com/view/ruxolitinib-discontinuation-at-conditioning-does-not-increase-gvhd-risk-in-myelofibrosis