FLT3

ASCO 2019 | Differences in treatment approaches to FLT3-mutated acute myeloid leukemia between Europe and the United States

On Saturday, May 31 2019, during the American Society for Clinical Oncology (ASCO) annual meeting in Chicago, US, Eytan Stein from Memorial Sloan Kettering Cancer Center, New York, US, outlined the differences in treating patients with FLT3-mutated acute myeloid leukemia (AML) between Europe and the United States (US).1

Dr Stein started by stating that overall survival (OS) for younger patients with AML has dramatically improved in the last 50 years, mostly due to the increased use of allogeneic stem cell transplantation (allo-SCT) and improved care options. However, for the majority of elderly patients, outcome has changed very little.2

A great advancement in the care of patients with AML has been the identification of certain genetic alterations which can predict outcome to treatment, such as; CEBPA and NMP1 (favorable risk group), FLT3-ITD (favorable to intermediate risk group) and RUNX1, ASXL1 and p53 (adverse risk group). However, it should be noted that the survival data used to predict outcome have been mostly obtained from studies which use standard chemotherapy regimens and need to be evaluated with caution.3

Dr Stein explained that the European Leukemia Network (ELN) recommends to assess allelic ratios of FLTwt and FLT-ITD when analyzing patients with FLT3-ITD AML. According to the ELN, patients with NPM1 mutation and a low FLT3-ratio (<0.5) can be categorized to the favorable risk group and should receive chemotherapy consolidation only. In contrast, patients with NPM1 mutation and a high FLT3 ratio (>0.5) should be considered for allo-SCT4.

Dr Stein proceeded to critically review the data on which the ELN recommendations are based on. He cited a study by Marta Pratcorona which was published in Blood, 2013, investigating the outcome of patients with co-occurring NPM1 and FLT3 mutations. Although patients with a low FLT3 ratio do slightly better that patients with a high FLT3 ratio, the long term survival remains below 50%. for both groups In addition, the accuracy of the FLT3 ratio assessment may differ between centers, as it is not standardized.5

In conclusion, Dr Stein recommended to refer all patients with FLT3-ITD for allo-SCT, independent of allelic ratio and co-occurring NPM1 mutation. Furthermore, he predicted that with the arrival of potent FLT3 inhibitors such as gilteritinib (in combination with chemotherapy or targeted therapies), the risk classification for patients with FLT3-ITD may change considerably.

The AML Global Portal (AGP) were pleased to interview Michael Heuser about the European position on the treatment of patients with FLT3-ITD AML. The link to this video can be found below in the expert opinion section.

References
  1. Stein E. Educational oral presentation: Use of molecular medicine to assess pretreatment prognosis of myeloid disorders. American Society for Clinical Oncology (ASCO) 2019, Chicago, US. 2019 May 31.
  2. Burnett A. et al. Therapeutic advances in acute myeloid leukemia. J Clin Onc. 2011 Feb 10. DOI: 10.1200/JCO.2010.30.1820.
  3. Yohe S. et al. Molecular Genetic Markers in Acute Myeloid Leukemia. J Clin Med. 2015 Mar. DOI: 10.3390/jcm4030460
  4. Dohner H. et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017. DOI: 10.1182/blood-2016-08-733196.
  5. Pratcorona M. et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood. 2013. DOI: 10.1182/blood-2012-06-431122

Expert Opinion

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