Genetic variation at HLA-B -21 may determine the antileukemic efficacy of activated natural killer (NK) cells and could be associated with a clinical difference during NK cell-activating immunotherapy, according to a study published in Blood.

Dimorphism at position -21 of HLA-B determines which inhibitory receptor will primarily regulate NK cell function. The study compared the functions of NK cells in subjects carrying HLA-B -21M or -21T using interleukin (IL)-2-activated NK cells and leukemic cells from patients with acute myeloid leukemia (AML). Furthermore, the researchers assessed the effect of this genetic variation on leukemia-free and overall survival in a phase 4 trial (ClinicalTrials.gov Identifier: NCT01347996) in which patients received IL-2-based immunotherapy.

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For the single-arm, multicenter study, 84 patients with AML in first complete remission were enrolled. Patients received 10 consecutive 21-day cycles of twice daily, subcutaneous histamine dihydrochloride (0.5 mg), as well as twice daily, subcutaneous, low-dose IL-2 (16,400 IU/kg) for 18 months or until relapse or death.

Subjects carrying HLA-B -21M harbored more reactive, better educated NKG2A+ NK cells, which were better able to degranulate lytic granules against killer cell immunoglobulin-like receptor (KIR) ligand-matched primary leukemic blasts (P <.05).

Following up on this result, the researchers found that the -21M variant was associated with longer leukemia-free survival (P =.04) and overall survival (P =.007) compared with the -21T variant during IL-2-based immunotherapy.

Reference

1.     Hallner A, Bernson E, Hussein BA, et al. The HLA-B-21 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia [published online March 28, 2019]. Blood. doi:10.1182/blood-2018-09-874990