Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy

• DOI: 10.1007/s00277-025-06204-5
• Publication Date: 2025-01-20T08:39:55Z
• Authors: Francesca Palandri; Filippo Branzanti; Erika Morsia; Alessandra Dedola; Giulia Benevolo; Mario Tiribelli; Eloise Beggiato; Mirko Farina; Bruno Martino; Giovanni Caocci; Novella Pugliese; Alessia Tieghi; Monica Crugnola; Gianni Binotto; Francesco Cavazzini; Elisabetta Abruzzese; Alessandro Isidori; Emilia Scalzulli; Domenico D’Agostino; Santino Caserta; Antonella Nardo; Roberto Massimo L...; Daniela Cilloni; Monica Bocchia; Fabrizio Pane; Florian H. Heidel; Giuseppe A. Palumbo; Massimo Breccia; Elena M. Elli; Massimiliano Boni...
• Keywords: Ruxolitinib; Janus kinase 2; Myeloproliferative neoplasm; Hematology

Abstract Calreticulin ( CALR ) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless driver mutations, splenomegaly symptoms generally treated JAK2 -inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the mutant clone have entered clinical investigation. To collect information on efficacy safety ruxolitinib -mutated patients, we report a sub-analysis “RUX-MF” (NCT06516406) study, comprising 135 786 ruxolitinib-treated patients. Compared to started more severe disease (higher peripheral blast counts, lower hemoglobin levels worse marrow fibrosis) after longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior who also had significantly rates symptom (56.1% 66.7%, = 0.04).