IFNα2 Reduces NET Levels in Myeloproliferative Neoplasms

Interferon-alpha2 (IFNα2) treatment may help reduce the risk of arterial and venous thrombosis in patients with myeloproliferative neoplasms (MPNs), according to a presentation at the 2022 American Society of Hematology Annual Meeting.

Previous research has indicated that neutrophil activation and formation of neutrophil extracellular traps (NETs) are involved in the development of MPNs and thrombosis, particularly cases involving the driver mutation JAK2 V617F. Laura Massarenti, of the Institute for Inflammation Research at Copenhagen University Hospital in Denmark, and colleagues sought to elucidate whether treatment with IFNα or hydroxyurea affects levels of circulating NETs in patients with MPNs.

The study included 128 patients who were enrolled in the phase III DALIAH trial and had one of four subtypes of MPN:

• Essential thrombocythemia (n=48)
• Polycythemia vera (PV) (n=61)
• Pre-myelofibrosis ( =10)
• Primary myelofibrosis (n=9)

The researchers compared the patients’ (a) baseline serum NET levels and (b) serum NET levels after 12 months of treatment with hydroxyurea or pegylated IFNα (PEG-IFNα2a or PEG-IFNα2b).

At baseline, the analysis found little difference among the four disease subtypes, among the various driver mutations involved (JAK2 V617F, CALR, MPL, or triple negative), or between patients who had a history of thromboses and those who did not. However, patients with PV and a JAK2 V617F allele burden of 50% or more at baseline had significantly higher baseline NET levels than those with an allele burden less than 50%. The researchers said they believe this indicates that the JAK/STAT pathway is involved in NET formation or clearance.

The study also found that baseline NET levels were significantly correlated with neutrophil count, neutrophil-to-lymphocyte ratio, and JAK2 V617F allele burden. That effect was not found at follow-up testing.

After 12 months of treatment, 77% of patients treated with PEG–IFNα-2a and 73% of those who received PEG-IFNα-2b had decreased NET levels, compared to 53% of patients treated with hydroxyurea.

Reference

Massarenti L, Knudsen TA, Enevold C, et al. Interferon-alpha2 treatment reduces circulating neutrophil extracellular trap levels in myeloproliferative neoplasms. Abstract #1680. Presented at the 64th ASH (American Society of Hematology) Annual Meeting and Exposition, December 10-13, 2022.