Contributions
Abstract: PB2129
Type: Publication Only
Background
Natural killer (NKs) cells provide rapid responses to viral-infected and malignant cells, including Multiple Myeloma (MM) cells. The balance among inhibitory and activating signals, delivered by multiple interactions between ligands (NKRL) on target cells and NK receptors (KIR), determines the posture of the NK cell response to either one of target cell elimination or tolerance.
Despite novel therapeutic options, 15% to 20% of newly-diagnosed MM patients experience early death and rapid relapse following or even during initial induction therapy, the majority of them carrying high-risk cytogenetics (HRC) features, such as del (17p), del (1p), t(4;14) or t(14;16), as detected by FISH.
Aims
The aim of this work was to study the influence of the differential expression of activating or inhibitory KIR and the inhibitory HLA class I ligands on clinical outcome of HRY-MM patients treated up-front with regimens followed or not by lenalidomide maintenance.
Methods
KIR expression, KIR haplotype AA/Bx, and their HLA ligands were determined in 31 healthy subjects (controls) and 69 MM patients using the Genotyping SSP and SSO kit.
In 50 HRY-MM patients (median age 54.1 years, 30 males), carrying at diagnosis del (17p), t(4;14) or t(14;16) and who were randomly assigned to lenalidomide maintenance until progression or observation after one autologous stem cell transplantation, we evaluated the role of KIR expression, KIR haplotype AA/Bx, and their HLA ligands on progression free survival (PFS).
Results
We observed that presence of KIR3DL1-edu was significantly more prevalent among controls as compared to MM patients (76,7% vs 43,5,9%, p<0,0023).
After median follow-up of 45 months, HRY-MM-patients carrying on KIR3DL1-edu had longer PFS than those without it (53.8 versus 41.5 months, p=0.08), without significant impact on overall survival (OS).
In MM patients the AA and Bx genotype frequencies were 24,6% (AA) and 74,4% (B/x) with an A:B ratio of 1:3.05. Among the healthy controls, the AA and B/x genotype frequencies were 33% and 67% with an A:B ratio of 1:2.
There was no significant difference in KIR haplotype AA/Bx frequencies in MM versus healthy subjects, however, in HRY-MM-patients, B/x haplotype was associated to longer PFS (56.4 versus 27.8 months, p=0.06). In multivariate analysis, only complete remission achievement after induction and consolidation treatment were predictors of outcome, independently from KIR and haplotype genetics.
Conclusion
Our data show that 3DL1-edu and B/x haplotype are associated to clinical outcome in HRY-MM-patients receiving a lenalidomide based approach, implying a role of NK cytotoxicity against MM residual cells. These data will be confirmed in larger prospective series.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): KIR, Multiple Myeloma, Natural killer, Therapy
Abstract: PB2129
Type: Publication Only
Background
Natural killer (NKs) cells provide rapid responses to viral-infected and malignant cells, including Multiple Myeloma (MM) cells. The balance among inhibitory and activating signals, delivered by multiple interactions between ligands (NKRL) on target cells and NK receptors (KIR), determines the posture of the NK cell response to either one of target cell elimination or tolerance.
Despite novel therapeutic options, 15% to 20% of newly-diagnosed MM patients experience early death and rapid relapse following or even during initial induction therapy, the majority of them carrying high-risk cytogenetics (HRC) features, such as del (17p), del (1p), t(4;14) or t(14;16), as detected by FISH.
Aims
The aim of this work was to study the influence of the differential expression of activating or inhibitory KIR and the inhibitory HLA class I ligands on clinical outcome of HRY-MM patients treated up-front with regimens followed or not by lenalidomide maintenance.
Methods
KIR expression, KIR haplotype AA/Bx, and their HLA ligands were determined in 31 healthy subjects (controls) and 69 MM patients using the Genotyping SSP and SSO kit.
In 50 HRY-MM patients (median age 54.1 years, 30 males), carrying at diagnosis del (17p), t(4;14) or t(14;16) and who were randomly assigned to lenalidomide maintenance until progression or observation after one autologous stem cell transplantation, we evaluated the role of KIR expression, KIR haplotype AA/Bx, and their HLA ligands on progression free survival (PFS).
Results
We observed that presence of KIR3DL1-edu was significantly more prevalent among controls as compared to MM patients (76,7% vs 43,5,9%, p<0,0023).
After median follow-up of 45 months, HRY-MM-patients carrying on KIR3DL1-edu had longer PFS than those without it (53.8 versus 41.5 months, p=0.08), without significant impact on overall survival (OS).
In MM patients the AA and Bx genotype frequencies were 24,6% (AA) and 74,4% (B/x) with an A:B ratio of 1:3.05. Among the healthy controls, the AA and B/x genotype frequencies were 33% and 67% with an A:B ratio of 1:2.
There was no significant difference in KIR haplotype AA/Bx frequencies in MM versus healthy subjects, however, in HRY-MM-patients, B/x haplotype was associated to longer PFS (56.4 versus 27.8 months, p=0.06). In multivariate analysis, only complete remission achievement after induction and consolidation treatment were predictors of outcome, independently from KIR and haplotype genetics.
Conclusion
Our data show that 3DL1-edu and B/x haplotype are associated to clinical outcome in HRY-MM-patients receiving a lenalidomide based approach, implying a role of NK cytotoxicity against MM residual cells. These data will be confirmed in larger prospective series.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): KIR, Multiple Myeloma, Natural killer, Therapy