[Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option]

Dtsch Med Wochenschr. 2010 Sep;135(38):1852-6. doi: 10.1055/s-0030-1247870. Epub 2010 Aug 25.
[Article in German]

Abstract

Background: The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status. The clinical value of a targeted intervention using the FLT3-ITD-specific inhibitor sorafenib in this situation is largely unknown.

Patients and methods: Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n=4) and after allogenic SCT (n=5) were treated off-label with sorafenib.

Results: All patients showed rapid hematological responses. There were three complete molecular remissions when sorafenib was given after allogenic SCT. Two of them are ongoing for 12 and 15 months, respectively. Long-term remissions after prior allogenic SCT were associated with the re-establishment of a chronic graft versus host reaction. Side effects could be controlled by dose reduction.

Conclusion: Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML. In the context of a prior allogenic SCT it may have curative potential via inducing a synergism between targeted inhibition of FLT3-ITD and anti-leukemic immunity.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Benzenesulfonates / therapeutic use*
  • Benzenesulfonates / toxicity
  • Combined Modality Therapy
  • DNA Mutational Analysis*
  • Dose-Response Relationship, Drug
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Off-Label Use*
  • Phenylurea Compounds
  • Pyridines / therapeutic use*
  • Pyridines / toxicity
  • Remission Induction
  • Retreatment
  • Sorafenib

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Sorafenib