{"title":"Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis","authors":"Francesca Palandri , Massimo Breccia , Erika Morsia , Elena M. Elli , Giulia Benevolo , Mario Tiribelli , Eloise Beggiato , Mirko Farina , Giovanni Caocci , Novella Pugliese , Alessia Tieghi , Monica Crugnola , Gianni Binotto , Francesco Cavazzini , Elisabetta Abruzzese , Alessandro Isidori , Alessandra Dedola , Alessandra Iurlo , Roberto M. Lemoli , Daniela Cilloni , Filippo Branzanti","doi":"10.1016/j.clml.2025.02.015","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Patients and Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 × 10<sup>9</sup>/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).</div><div>After ruxolitinib discontinuation, 3-year OS was 33.4% in severely cytopenic and 54.4% in myeloproliferative patients (<em>P</em> < .001); this was confirmed after adjustment for risk categories. Noncytopenic and mildly anemic patients had comparable OS (<em>P</em> = .73). Patients with large splenomegaly had significantly poorer OS compared to nonsplenomegalic patients (OS: 33.5% vs. 51.6% <em>P</em> = .01). Large splenomegaly confirmed its negative prognostic impact on OS of patients with myeloproliferative MF (60.7% vs. 44.5%, <em>P</em> = .05). In patients with severe cytopenia, the presence of a large splenomegaly did not influence OS (41.7% vs. 26.1%, <em>P</em> = .26).</div></div><div><h3>Conclusions</h3><div>Cytopenic phenotype and large splenomegaly in myeloproliferative MF are key prognostic determinants of outcome after ruxolitinib discontinuation.</div></div>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":"25 7","pages":"Pages e524-e532.e3"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Lymphoma, Myeloma & Leukemia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2152265025000771","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed monthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma & Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.