Combination Therapy Works Better in AML Patients With Activated NK Cells

The presence of natural killer cells can help keep acute myeloid leukemia (AML) in remission in patients treated with a combination therapy, according to a recent study.


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The interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I play an important role in regulating natural killer cells and protecting normal tissue from cell attack. A substantial amount of people have a ‘missing ligand’ genotype, meaning they lack ligands for inhibitory KIRs. Limited data exist regarding how these genotypes impact patients with untransplanted AML.

Fredrik Bergh Thorén, PhD, University of Gothenburg (Sweden), and colleagues sought to explore this impact further. They determined natural killer cell phenotypes and KIR/HLA genotypes in 81 patients with AML who had received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention. Among these patients, 60% had natural cells that were active against leukemia.

Positive clinical outcomes were observed among patients with natural killer cells who received the Ceplene/IL-2 combination therapy, especially among patients harboring functional natural killer cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Sixty-seven percent of patients with natural killer cells remained in remission for at least 2 years and had an improved quality of life, compared with 11% of those without natural killer cells. However, the clinical benefit of high NCR expression was observed only in patients with a missing ligand genotype and/or a KIR B/x genotype.

Ultimately, the researchers concluded that functional natural killer cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor natural killer cell autoreactivity. Additionally, natural killer cell profiling may contribute to optimally select patients who are suitable for treatment.

“These results imply that potentially a large proportion of AML patients harbor efficacious anti-leukemic natural killer cells that are activated during immunotherapy with Ceplene in combination with low-dose IL-2,” said Dr Thorén in a press release (August 1, 2017).–Christina Vogt