Simple SummaryBone marrow fibrosis (BMF) is a hallmark of myelofibrosis (a rare blood cancer), and BMF severity may be useful in predicting patient response to treatment, since high-severity BMF is associated with poor survival. In this study, we studied how BMF severity and early (within 2 years of diagnosis) versus late (more than 2 years after diagnosis) initiation of ruxolitinib treatment affected the response to treatment in patients with primary myelofibrosis. Our results showed that patients with low-severity BMF had a better response to treatment with ruxolitinib and longer survival; however, all patients treated with ruxolitinib showed improvements in spleen size and survival, regardless of their BMF severity. Our data also showed that initiation of early treatment with ruxolitinib resulted in better responses in all patients. This study showed that treatment with ruxolitinib can benefit patients with both low- and high-severity BMF, especially when it is started early.AbstractBone marrow fibrosis (BMF) is an adverse prognostic factor for myelofibrosis (MF). The single-arm, open-label, phase 3b JUMP trial (NCT01493414) assessed the safety and efficacy of the JAK1/JAK2 inhibitor ruxolitinib in patients with symptomatic MF. This post hoc analysis investigated the impact of BMF grade on response and outcomes in patients with primary MF (PMF) from the JUMP study. BMF was assessed by biopsy and graded from 0 to 3; grades 0–1 were considered low-grade fibrosis (LGF) and grades 2–3 were considered high-grade fibrosis (HGF). Patients with LGF (n = 268) had lower rates of cytopenias at baseline but showed comparable disease burden vs. patients with HGF (n = 852). The proportion of patients achieving a spleen response was greater in the LGF group vs. the HGF group at Week 24 and at any time during the study, while overall survival estimates were improved in patients with LGF vs. patients with HGF. Early initiation of ruxolitinib therapy (within 2 years of diagnosis) was associated with increased response rates in all patients. These results highlight the efficacy of ruxolitinib in symptomatic patients with PMF, with the greatest clinical improvements observed in patients with LGF and in patients who received early treatment.