Clinical characteristics and driver mutations in patients with ET ± JAK2V617F and/or CALR mutations

Results from a single-center, cross-sectional registry analysis, comparing clinical features, outcomes, and potential driver mutations in patients with essential thrombocythemia (ET) with and without JAK2^V617F and/or CALR mutations, were published in Hematology by Thammayot et al. The analysis included 162 patients diagnosed with ET between 2007 and 2024 (JAK2 mutated, n = 99; JAK2/CALR unmutated, n = 39); whole exome sequencing (WES) was performed in a subset of patients with JAK2^V617F/CALR-unmutated disease (n = 15). The primary objective was to compare clinical characteristics and outcomes of patients with and without JAK2^V617F and CALR mutations. The secondary objective was to identify potential driver mutations in patients with unmutated disease using WES. 

Key data: Patients with JAK2^V617F/CALR-unmutated ET were significantly younger than those with JAK2^V617F-mutated ET (mean, 53.7 vs 61.1 years; p = 0.012). The overall response rate (ORR) was 79% in patients with JAK2^V617F/CALR-unmutated ET vs 88% in those with JAK2^V617F-mutated disease, while the rate of treatment non-response was significantly higher with unmutated ET (30.77% vs 11.11%; p = 0.02). There were no significant differences in the rates of hydroxyurea (HU) intolerance/resistance, progression to myelofibrosis (MF), leukemic transformation, new thrombotic events, or new bleeding between the mutated and unmutated cohorts, while secondary malignancy was more common in patients with unmutated disease (p = 0.02). With a median follow-up of 159.6 months, median overall survival (OS) was similar between patients with vs without JAK2^V617F and/or CALR mutations (12.6 years vs 13.5 years, respectively; p = 0.63). Among 15 patients with JAK2^V617F/CALR-unmutated ET and selected for WES, somatic variants were detected in 93.3%. Changes in CALR and MPL were among potential driver mutations identified.  

Key learning: Overall, clinical characteristics and outcomes were largely comparable between patients diagnosed with ET with and without JAK2^V617F and/or CALR mutations, while WES identified additional candidate driver mutations in patients with JAK2^V617F/CALR-unmutated ET. These findings support consideration of broader genomic profiling to improve molecular classification and inform longitudinal monitoring in this setting.