Is AML NPM1^mut a candidate for immune checkpoint inhibition?

On 21^st September 2017, in a Letter to the Editor of  Haematologica, Jochen Greiner et al. from the University of Ulm, Germany, reported results of their study which evaluated whether mutated Nucleophosmin 1 (NPM1^mut) Acute Myeloid Leukemia (AML) patients might be candidates  for Programmed Death 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) directed immune checkpoint inhibition.

Peripheral Blood (PB) samples from NPM1^mut (n = 15) and NPM1 Wild-Type (NPM1^wt [n = 15]) AML patients at diagnosis were assessed for PD-L1 expression in leukemic cells including the Leukemic Stem Cells (LSCs) compartment using flow cytometry and microarray analysis.

The key results of the study were:

• Median PD-L1 expression in bulk AML cells was significantly higher in NPM1^mut patients compared to NPM1^wt patients; 1.4% (range, 0.0–8.5%) vs 0.3% (range, 0.0–1.1%) positive cells, P < 0.0001
• PD-L1 expression was detected significantly at a higher percentage in the LSCs in NPM1^mut AML than in NPM1^wt AML; 3.6% (range, 0.0–17.2%) vs 0.3% (range, 0.0–3.0%) positive cells, P < 0.001
• PD-L1 positive LSCs of NPM1^mut AML samples had a significant expression of mutant NPM1

In summary, PD-L1 expression was higher in NPM1^mut patients particularly in the LSCs compartment compared to NPM1^wt AML cases.

The authors concluded by noting that in NPM1^mut AML cases, “the immunogenicity of neoantigens derived from the NPM1 mutation and the higher PD-L1 expression constitute a promising target structures for individualized immunotherapeutic approaches”.