Table 1.

Proposed classification scheme for response to FLT3 inhibitors used as single agents in patients with relapsed/refractory FLT3/ITD acute myeloid leukemia (AML), based on what is known about the clinical characteristics of the study population and mechanism of action of FLT3 inhibitors.

No response	Persistent blasts in the bone marrow aspirate (Wright–Giemsa stain) and/or core sample, with characterization of leukemia-associated phenotype by multi-parameter flow cytometry, comprising ≥ 20% of total cellularity, corresponding to the 2008 WHO classification of acute myeloid leukemia
Minor response	Absence of circulating blasts in the peripheral blood Persistent marrow blasts ≥ 5% but < 20% of total cellularity FLT3-mutant allele detectable by polymerase chain reaction (PCR) from a bone marrow aspirate sample
Major response	Absence of circulating blasts in the peripheral blood Minimal residual disease, blasts < 5% of total marrow cellularity FLT3-mutant allele detectable by PCR from a bone marrow aspirate sample
Major molecular response	Absence of circulating blasts in the peripheral blood No morphologic evidence of leukemia by morphology or flow cytometry FLT3-mutant allele not detectable by PCR from a bone marrow aspirate sample

This classification scheme is independent of any platelet or red cell transfusion requirements. The categories of No Response and Minor Response essentially amount to the persistence of disease that is readily discernible by conventional light microscopic techniques. A Major Response is the reduction of the tumor burden to a minimal residual disease (MRD) state, in which the presence of the FLT3/ITD clone is detectable only with multi-parameter flow cytometry and PCR. A Major Molecular Response indicates the absence of any detectable evidence of the FLT3/ITD clone by any conventionally available methodologies. The latter two categories would be expected to be associated with clinical benefit, a hypothesis which could be tested in well-designed randomized trials using overall survival as an end point.

FLT3: FMS-like tyrosine kinase-3; ITD: Internal tandem duplications.