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Benefits and pitfalls of Peg-Interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis, a French Intergroup of Myeloproliferative neoplasms (FIM) study.

Benefits and pitfalls of Peg-Interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis, a French Intergroup of Myeloproliferative neoplasms (FIM) study.
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Ianotto JC, Chauveau A, Boyer-Perrard F, Gyan E, Laribi K, Cony-Makhoul P, Demory JL, de Renzis B, Dosquet C, Rey J, Roy L, Dupriez B, Knoops L, Legros L, Malou M, Hutin P, Ranta D, Benbrahim O, Ugo V, Lippert E, Kiladjian JJ,


Ianotto JC, Chauveau A, Boyer-Perrard F, Gyan E, Laribi K, Cony-Makhoul P, Demory JL, de Renzis B, Dosquet C, Rey J, Roy L, Dupriez B, Knoops L, Legros L, Malou M, Hutin P, Ranta D, Benbrahim O, Ugo V, Lippert E, Kiladjian JJ, (click to view)

Ianotto JC, Chauveau A, Boyer-Perrard F, Gyan E, Laribi K, Cony-Makhoul P, Demory JL, de Renzis B, Dosquet C, Rey J, Roy L, Dupriez B, Knoops L, Legros L, Malou M, Hutin P, Ranta D, Benbrahim O, Ugo V, Lippert E, Kiladjian JJ,

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Haematologica 2017 12 07() pii haematol.2017.181297
Abstract

We have previously described the safety and efficacy of pegylated interferon-α2a therapy in a cohort of sixty-two patients with myeloproliferative neoplasm-associated myelofibrosis followed 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 pegylated interferon initiation was 58 months. At time of analysis, 30 (48.4%) patients were alive including 16 still treated with pegylated interferon. The median survival of patients with intermediate and high-risk prognostic Lille and DIPSS scores treated with pegylated interferon was increased in comparison to historical cohorts. In addition, overall survival was significantly correlated with the duration of pegylated interferon therapy (70 vs. 30 months after two years of treatment, p<10-12). JAK2V617F allele burden was decreased by more than 50% in 58.8% of patients and 2 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 survivals. These findings in a large series of patients with myelofibrosis suggest that pegylated interferon therapy may provide a survival benefit for intermediate or high-risk Lille and DIPSS score patients. It also reduced the JAK2V617F allele burden in most patients. These results further support the use of pegylated interferon in selected patients with myelofibrosis.(Clinicaltrials.gov #NCT02910258 and #NCT02897297).

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