FLT3|NPM1

Molecular response in AML patients with NPM1 and FLT3 mutations undergoing SCT

This month, in a Letter to the Editor of Bone Marrow Transplantation, Rana Salem and colleagues from the American University of Beirut Medical Center (AUBMC), reported results from their retrospective study which evaluated the dynamics of molecular response to treatment in adult Acute Myeloid Leukemia (AML) patients with concomitant Nucleophosmin-1 (NPM1) and Fms Like Tyrosine Kinase 3 (FLT3) mutations at diagnosis and after allogenic Stem Cell Transplantation (SCT).  

Twelve de novo AML patients (median age = 45 years) with concomitant NPM1 and FLT3 mutations, who were treated at the AUBMC between January 2011 to December 2016 were included in this retrospective study. Ten patients received allogenic SCT followed by post-transplant sorafenib (tyrosine kinase inhibitor) maintenance. Bone marrow samples were tested for FLT3 and NPM1 gene expression at diagnosis, after induction, after each consolidation, before and at days 30, 60 and 100 after allogenic SCT.

The key results of the study were:
  • After induction, FLT3 was negative in all patients (n = 12) and only two patients (2/12) were negative for NPM1 mutation
  • After first consolidation, FLT3 mutation remained negative in 11 patients with molecular relapse occurring in one patient
  • After first consolidation, NPM1 mutation was negative in three patients and in seven additional patients after allogenic SCT (before sorafenib [n = 4] and after sorafenib [n = 3])
  • No molecular positivity for FLT3 was noted after second consolidation or after allogenic SCT
  • NPM1 Minimal Residual Disease (MRD) value was elevated in patients (3/4) with quantitative assessment at diagnosis and after induction

In summation, “FLT3 becomes negative early after induction while NPM1 mutation negatively lags behind and may become negative after sorafenib”.

The authors concluded by suggesting that NPM1 mutation is a potential candidate for MRD evaluation post allogenic SCT. They further proposed that the findings of their study should be validated in a large prospective study.

References
  1. Salem R. et al. Dynamics of molecular response in AML patients with NPM1 and FLT3 mutations undergoing allogeneic stem cell transplant. Bone Marrow Transplant. 2017 Aug; 52(8): 1187–1190. DOI: 10.1038/bmt.2017.82. [Epub 2017 Jun 5].