Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation. To collect information on efficacy and safety of ruxolitinib in CALR-mutated patients, we report a sub-analysis of the “RUX-MF” (NCT06516406) study, comprising 135 CALR-mutated and 786 JAK2-mutated ruxolitinib-treated patients. Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).
Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy / Palandri, Francesca; Branzanti, Filippo; Morsia, Erika; Dedola, Alessandra; Benevolo, Giulia; Tiribelli, Mario; Beggiato, Eloise; Farina, Mirko; Martino, Bruno; Caocci, Giovanni; Pugliese, Novella; Tieghi, Alessia; Crugnola, Monica; Binotto, Gianni; Cavazzini, Francesco; Abruzzese, Elisabetta; Isidori, Alessandro; Scalzulli, Emilia; D'Agostino, Domenico; Caserta, Santino; Nardo, Antonella; Lemoli, Roberto Massimo; Cilloni, Daniela; Bocchia, Monica; Pane, Fabrizio; Heidel, Florian H.; Palumbo, Giuseppe A.; Breccia, Massimo; Elli, Elena M.; Bonifacio, Massimiliano. - In: ANNALS OF HEMATOLOGY. - ISSN 0939-5555. - 104:1(2025), pp. 241-251. [10.1007/s00277-025-06204-5]
Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy
Tiribelli, Mario;Scalzulli, Emilia;Pane, Fabrizio;Breccia, Massimo;
2025
Abstract
Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation. To collect information on efficacy and safety of ruxolitinib in CALR-mutated patients, we report a sub-analysis of the “RUX-MF” (NCT06516406) study, comprising 135 CALR-mutated and 786 JAK2-mutated ruxolitinib-treated patients. Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
