Incidence of blast phase in myelofibrosis patients according to anemia severity at ruxolitinib start and during therapy

Abstract

AbstractBackgroundAnemia is frequently present in patients with myelofibrosis (MF), and it may be exacerbated by treatment with the JAK2‐inhibitor ruxolitinib (RUX). Recently, a relevant blast phase (BP) incidence has been reported in anemic MF patients unexposed to RUX.MethodsThe authors investigated the incidence of BP in 886 RUX‐treated MF patients, included in the “RUX‐MF” retrospective study.ResultsThe BP incidence rate ratio (IRR) was 3.74 per 100 patient‐years (3.74 %p‐y). At therapy start, Common Terminology Criteria for Adverse Events grade 3‐4 anemia (hemoglobin [Hb] <8 g/dL) and severe sex/severity‐adjusted anemia (Hb <8/<9 g/dL in women/men) were present in 22.5% and 25% patients, respectively. IRR of BP was 2.34 in patients with no baseline anemia and reached respectively 4.22, 4.89, and 4.93 %p‐y in patients with grade 1, 2, and 3–4 anemia. Considering the sex/severity‐adjusted Hb thresholds, IRR of BP was 2.85, 4.97, and 4.89 %p‐y in patients with mild/no anemia, moderate, and severe anemia. Transfusion‐dependent patients had the highest IRR (5.03 %p‐y). Progression‐free survival at 5 years was 70%, 52%, 43%, and 27% in patients with no, grade 1, 2, and 3–4 anemia, respectively (p < .001). At 6 months, 260 of 289 patients with no baseline anemia were receiving ruxolitinib, and 9.2% had developed a grade 3–4 anemia. By 6‐month landmark analysis, BP‐free survival was significantly worse in patients acquiring grade 3–4 anemia (69.3% vs. 88.1% at 5 years, p < .001).ConclusionsThis study highlights that anemia correlates with an increased risk of evolution into BP, both when present at baseline and when acquired during RUX monotherapy. Innovative anemia therapies and disease‐modifying agents are warranted in these patients.