Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma

Abstract

Abstract Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1+ (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1+ compared with KIR3DS1− was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1+ in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1+KIR3DL1+HLA-Bw4− had a significantly shorter PFS than patients who were KIR3DS1−, translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR–human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.