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

Cancer. 2024 Apr 15;130(8):1270-1280. doi: 10.1002/cncr.35156. Epub 2023 Dec 28.

Abstract

Background: Anemia 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.

Methods: The authors investigated the incidence of BP in 886 RUX-treated MF patients, included in the "RUX-MF" retrospective study.

Results: The 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).

Conclusions: This 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.

Keywords: anemia; blast phase; myelofibrosis; ruxolitinib.

MeSH terms

  • Anemia* / chemically induced
  • Anemia* / epidemiology
  • Blast Crisis
  • Female
  • Hemoglobins
  • Humans
  • Incidence
  • Male
  • Nitriles
  • Primary Myelofibrosis* / drug therapy
  • Pyrazoles*
  • Pyrimidines*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • ruxolitinib
  • Nitriles
  • Hemoglobins
  • Pyrazoles
  • Pyrimidines