Statins Enhance the Efficacy of Pegylated Interferon-α2 in Philadelphia-Negative Chronic Myeloproliferative Neoplasms

Chronic inflammation may be a key driving force in the development and progression of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Statins, commonly used to lower cholesterol, also possess anti-proliferative, proapoptotic and anti-inflammatory properties, that may be beneficial in the treatment of MPN patients. This retrospective cohort study investigated whether statin use, in addition to standard cytoreductive therapy, shortens the time required to achieve hematological and molecular responses while allowing for lower cytoreductive drug dosages. A total of 129 patients were included, with 53 receiving statins from diagnosis. The study found that statin users achieved complete hematologic response (CHR) significantly faster than non-users (median time: 8 versus 18 months; HR 2.1, 95%CI 1.4-3.1, P = 0.0003). Among patients treated with pegylated interferon-alpha2 (IFN), the CHR rate was 97% in statin users versus 83% in non-users (HR 2.5, 95%CI 1.5-3.9, P = 0.0004), and a higher proportion of statin users sustained CHR throughout follow-up. Additionally, IFN-treated statin users received a significantly lower mean dose of IFN. A dose-response relationship was observed, with higher statin intensity associated with an increase of CHR. Furthermore, statin use was significantly associated with achieving a partial molecular response among IFN-treated patients (HR 2.6, 95%CI: 1.1-6.0, P = 0.029). No significant association was observed in hydroxyurea-treated patients. These findings suggest that statins may enhance the efficacy of IFN in MPN patients, while their benefit in hydroxyurea-treated patients remains unclear. Prospective studies are warranted to further explore the therapeutic potential of statins in MPNs.