Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis

Introduction: In patients with myelofibrosis (MF), overall survival (OS) after ruxolitinib discontinuation is poor, with leukemic transformation, clonal evolution and thrombocytopenia as the main factors worsening prognosis. Patients and methods: To assess the impact of disease phenotype on outcome after ruxolitinib discontinuation in chronic phase patients, we performed a sub-analysis of the "RUX-MF" study (NCT06516406), which now includes 1055 MF patients who received ruxolitinib in a real-life context. Results: After a median follow-up of 3.3 years, 397 patients discontinued ruxolitinib therapy while in chronic phase. At treatment end, 208 patients (52.4%) had a severely cytopenic phenotype (defined as platelets < 100 × 109/L and/or hemoglobin < 8 g/dL); among the remaining myeloproliferative 189 patients, 97 had no cytopenia (51.3%) and 92 (48.7%) had mild anemia only (hemoglobin between 8 and 10 g/dL). Overall, 175 patients (44.1%) had a large splenomegaly (palpable at ≥ 10 cm below costal margin). After ruxolitinib discontinuation, 3-year OS was 33.4% in severely cytopenic and 54.4% in myeloproliferative patients (P < .001); this was confirmed after adjustment for risk categories. Noncytopenic and mildly anemic patients had comparable OS (P = .73). Patients with large splenomegaly had significantly poorer OS compared to nonsplenomegalic patients (OS: 33.5% vs. 51.6% P = .01). Large splenomegaly confirmed its negative prognostic impact on OS of patients with myeloproliferative MF (60.7% vs. 44.5%, P = .05). In patients with severe cytopenia, the presence of a large splenomegaly did not influence OS (41.7% vs. 26.1%, P = .26). Conclusions: Cytopenic phenotype and large splenomegaly in myeloproliferative MF are key prognostic determinants of outcome after ruxolitinib discontinuation.