Benefits and pitfalls of pegylated interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of Myeloproliferative neoplasms (FIM) study

We have previously described the safety and efficacy of pegylated interferon-α2a therapy in a cohort of 62 patients with myeloproliferative neoplasm-associated myelofibrosisfollowed in centers affiliated to the French Intergroup of Myeloproliferative neoplasms. In this study, we report their long-term outcomes and correlations with mutational patterns of driver and non-driver mutations analyzed by targeted next generation sequencing. The median age at diagnosis was 66 years old, the median follow-up since starting pegylated interferonwas 58 months. At the time of analysis, 30 (48.4%) patients were alive including 16 still being treated with pegylated interferon. The median survival of patients with intermediate and high-risk prognostic Lille and dynamic International Prognostic Scoring Systemscores treated with pegylated interferonwas increased in comparison to that of historical cohorts. In addition, overall survival was significantly correlated with the duration of pegylated interferontherapy (70 versus 30 months after 2 years of treatment, P −12 ). JAK2 V617F allele burden was decreased by more than 50% in 58.8% of patients and two patients even achieved complete molecular response. Next-generation sequencing analyses performed in 49 patients showed that 28 (57.1%) of them carried non-driver mutations. The presence of at least one additional mutation was associated with a reduction of both overall and leukemia-free survival. These findings in a large series of patients with myelofibrosissuggest that pegylated interferontherapy may provide a survival benefit for patients with intermediate- or high-risk Lille and dynamic International Prognostic Scoring Systemscores. It also reduced the JAK2 V617F allele burden in most patients. These results further support the use of pegylated interferonin selected patients with myelofibrosis.