Efficacy and Safety of Gilteritinib versus Sorafenib as Post-Transplant Maintenance in Patients With FLT3-ITD Acute Myeloid Leukemia

Clin Lymphoma Myeloma Leuk. 2024 Nov;24(11):e819-e826. doi: 10.1016/j.clml.2024.07.001. Epub 2024 Jul 25.

Abstract

Background: FLT3-ITD AML is associated with an increased risk of relapse, leading many patients to receive an allogeneic hematopoietic stem cell transplantation (alloHCT) after induction. Unfortunately, relapse rate after alloHCT remains high and strategies are needed to improve outcomes.

Materials and methods: We performed a retrospective analysis of adult patients with FLT3-ITD AML who received alloHCT from 6/1/2016 to 12/31/2020 and received gilteritinib (GILT) or sorafenib (SORA)as post-transplant maintenance, outside of a clinical trial.

Results: A total of 55 patients were treated with either GILT (n = 27) or SORA (n = 29) for post-HCT maintenance. One patient was treated with SORA after first alloHCT and GILT after second alloHCT. Patient characteristics were comparable between groups. FLT3 inhibitors were utilized in pre-alloHCT therapy in all but 1 patient. The median duration of time that patients remained on GILT was 385 days (range, 10-804) and on SORA 315 days (range, 3-1777). 1-year PFS and relapse incidence were similar between GILT and SORA; PFS was 66% versus 76% (P = .4) and relapse incidence was 19% versus 24% (P = .6), respectively.Both groups had high incidence of Grade 3-4 hematological toxicity, including neutropenia (45% GILT and 34% SORA) and thrombocytopenia (30% GILT and 52% SORA). Only 44% and 14% patients who received GILT and SORA did not discontinue maintenance, respectively.

Conclusion: Our results revealed comparable PFS and a similar toxicity profile when SORA and GILT are used as post- HCT maintenance therapy.

Keywords: AML; FLT3 inhibitors; FLT3-ITD; Maintenance; Stem cell transplant.

MeSH terms

  • Adult
  • Aged
  • Aniline Compounds* / adverse effects
  • Aniline Compounds* / pharmacology
  • Aniline Compounds* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazines* / pharmacology
  • Pyrazines* / therapeutic use
  • Retrospective Studies
  • Sorafenib* / pharmacology
  • Sorafenib* / therapeutic use
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • Sorafenib
  • fms-Like Tyrosine Kinase 3
  • gilteritinib
  • Aniline Compounds
  • FLT3 protein, human
  • Pyrazines
  • Protein Kinase Inhibitors