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

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).