Impact of ruxolitinib on survival of patients with myelofibrosis in the real world: update of the ERNEST Study

Abstract

Conflict of interest: COI declared -see note COI notes: PG reports speaker honoraria from Novartis and Abbvie and fees from Novartis and Abbvie for participation on advisory boards. AMV has personal fees as advisory bord and speaker fee from AOP Orphan Pharmaceuticals and Novartis. AR has personal fees as advisory board from Astellas, Amgen, Celgene BMS, Gilead, Italfarmaco, Novartis, Omeros, Roche, and Sanofi. TB declares personal fees as advisory bord from AOP Orphan Pharmaceuticals, Italfarmaco, and Novartis, outside the submitted work. The remaining authors declare no competing financial interests. Preprint server: No;Author contributions and disclosures: PG interpreted the data, and wrote the brief report. TB conceived and designed the study, supervised the analysis and critically revised the brief report. AG and AC contributed to dataset preparation, planned and performed statistical analyses. AM directed the project. AMV interpreted the data and critically revised the brief report.

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

“…15,16 An improvement of overall survival (OS) with RUX has been reported in a post-hoc pooled analysis of the registration trials, 17,18 in a comparison of phase 1/2 trial data with matched historical controls, 19 and in a recently reported registry study. 20 Nonetheless, RUX therapy is burdened by a substantial proportion of suboptimal responses, loss of response over time and significant discontinuation rates both in clinical trials 18,[21][22][23] and in the realworld setting. 24,25 Pre-RUX factors associated with lower spleen response rates include higher risk MF, large splenomegaly, transfusion-dependency, platelet count <200 x10 9 /L, a time-interval between MF diagnosis and RUX start >2 years, RUX as ≥2 nd line treatment, any genotype other than JAK2V617F with ≥50% allele burden, and ≥3 mutations identified by next-generation sequencing (NGS).…”

“… 15,16 An improvement of overall survival (OS) with RUX has been reported in a posthoc pooled analysis of the registration trials, 17,18 in a comparison of phase 1/2 trial data with matched historical controls, 19 and in a recently reported registry study. 20 …”

Does ruxolitinib really prolong survival in individuals with myelofibrosis? The never-ending story

“…We read with interest the recent article by Guglielmelli et al 1 in which they report new evidence showing ruxolitinib prolongs survival in individuals with myelofibrosis. The authors analyzed data from a registry of so-called real-world data from European centers.…”

“…Getting the survival question right is vital because it affects the decision of whether to recommend ruxolitinib therapy when the goal is prolonging survival rather than reducing splenomegaly or improving constitutional symptoms. Six additional studies 1 , 10-14 addressed the question of whether ruxolitinib or the cognate JAK2 inhibitor momelotinib improves survival, the latest of which is that by Guglielmelli et al. 1 Although designs of these studies differ, they are fundamentally case-control analyses ( Table 1 ).…”

“…Six additional studies 1 , 10-14 addressed the question of whether ruxolitinib or the cognate JAK2 inhibitor momelotinib improves survival, the latest of which is that by Guglielmelli et al. 1 Although designs of these studies differ, they are fundamentally case-control analyses ( Table 1 ). We have discussed limitations of case-control studies elsewhere.…”