Relationship between additional mutations at diagnosis and treatment response in patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) have a chronic evolution with a risk of hematologic transformation associated with a dismal outcome. Because patients with resistance or intolerance have adverse prognosis, it is important to identify which patient will respond to first-line treatment. We, therefore, aim to describe the association between additional mutations and response to first-line treatment in patients with ET. In this retrospective study, we analyzed the molecular landscape of 121 ET patients first-line treated with hydroxyurea (HU; n = 86) or pegylated interferon (peg-IFN; n = 35). Patients undergoing peg-IFN therapy were younger and had higher proportion of low and very low risk of thrombosis recurrence. A total of 62 patients (51%) had ≥1 additional mutations at diagnosis. At 12 months of treatment, 75 patients (62%) achieved complete response (CR), 37 (31%) partial response, and 7 (6%) no response. The presence of at least 1 additional mutation at diagnosis was associated with not achieving CR (hazard ratio [HR], 0.65; P = .038), whereas treatment with peg-IFN was associated with higher CR (HR, 2.00; P = .002). The number of additional mutations at diagnosis was associated with hematologic progressions (P < .0001). None of the patients receiving peg-IFN therapy progressed to myelofibrosis, whereas 16 of 86 patients (19%) treated with HU developed secondary myelofibrosis. In conclusion, our results suggest that the presence of at least 1 additional mutation at diagnosis is associated with failure to achieve CR and also with an increased risk of hematologic evolution.