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

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.

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.

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).

Cytopenic phenotype and large splenomegaly in myeloproliferative MF are key prognostic determinants of outcome after ruxolitinib discontinuation.