Rapid Hematological and Molecular Response to Pegylated Interferon in WHO-Defined Pre-Fibrotic Myelofibrosis

Background: Pre-fibrotic myelofibrosis (pre-PMF) is a rare subentity of myeloproliferative neoplasm (MPN) with limited overall survival and the potential for progression toward overt, symptomatic myelofibrosis or blastic transformation. To date, a consensus on the treatment of pre-PMF, especially in asymptomatic cases, has yet to be reached. Interferon therapy has been employed as an effective treatment for MPN for many decades, due to its immunomodulatory properties and disease-modifying effects. Methods: The objective of this monocentric study was to evaluate hematological, molecular, and clinical responses, as well as the overall outcome, to pegylated interferon (peginterferon) in pre-PMF cases harboring a JAK2 or CALR mutation. Results: In a cohort of 55 consecutive patients with a median follow-up period of 3.89 (1.63; 6.10) years, a high rate of complete hematological response (81%) was documented after 24 months. Deep molecular responses with a >50% reduction in allele burden were documented in 54.6% of the JAK2-mutated and 7.7% of CALR-mutated patients, respectively (p = 0.023). Concerning fibrosis, at least the stabilization of disease was achieved in 73% of evaluable patients. Furthermore, only one case of blastic transformation was observed, along with three cases of thromboembolic events in the JAK2-mutated cohort. Conclusions: The study confirms the substantial efficacy of interferon in pre-PMF patients with rapid hematological normalization in most patients. Molecular responses were striking, but largely confined to JAK2-mutated patients. To our knowledge, this is the largest retrospective cohort of strictly WHO-defined pre-PMF patients treated with interferon and observed for a reasonable duration of time.