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

Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NKcells 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. (Blood. 2010;116(12):2033-2039)