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

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.

Figure 1

Association between KIR3DS1 genotype and PFS. (A) PFS for GR patients who were KIR3DS1⁺ was significantly shorter than for GR patients who were KIR3DS1⁻ (P = .003). The median PFS for poor-risk patients was not significantly different from GR, KIR3DS1⁺ patients (P = .061). (B) Among patients with GR disease at ASCT, those with KIR3DS1⁺/KIR3DL1⁺/HLA-Bw4⁻ have significantly reduced PFS than patients with KIR3DS1⁺/KIR3DL1⁺/HLA-Bw4⁺ and patients with KIR3DS1⁻ irrespective of HLA-Bw4 (P = .002).