Neuroblastoma Patients’ KIR and KIR-Ligand Genotypes Influence Clinical Outcome for Dinutuximab-based Immunotherapy: A Report from the Children`s Oncology Group

Neuroblastoma Patients’ KIR and KIR-Ligand Genotypes Influence Clinical Outcome for Dinutuximab-based Immunotherapy: A Report from the Children`s Oncology Group
The use of dinutuximab-based immunotherapy has improved the outcome for patients with high-risk neuroblastoma in a phase III clinical trial (ANBL0032). Dinutuximab is an anti-GD2 monoclonal antibody whose activity is facilitated by NK cells. KIRs on NK cells highly polymorphic and, similar to HLA haplotypes, may have an effect on cellular immune response. This secondary analysis of ANBL0032 data investigated the association between KIR/KIR-ligand genotypes and clinical outcome in high risk neuroblastoma patients randomized to immunotherapy or no immunotherapy.
A total of 226 high-risk neuroblastoma patients were enrolled into ANBL0032 in 2010 and were randomized to immunotherapy or no immunotherapy; 176 patients had DNA available for genotyping for KIR/KIR-ligands (88 immunotherapy; 86 patients no immunotherapy).
Patients with the KIR/KIR-ligand genotypes “all KIR-ligands present”, “inhibitory KIR2DL2”, and “inhibitory KIR3DL1” were associated with improved event-free and overall survival with >5 years follow-up if patients had received immunotherapy versus no immunotherapy. The “complementary KIR/KIR-ligand” genotypes did not improve outcome in patients receiving immunotherapy compared to isotretinoin alone.
Prior studies on KIR/KIR-ligand genotyping showed conflicting results on the benefit of different KIR/KIR-ligand genotypes on outcome in neuroblastoma, therefore validation by independent clinical studies is needed.
High-risk neuroblastoma patients with certain KIR/KIR-ligand genotypes benefited from immunotherapy in this study. Validation of these findings is necessary, before KIR/KIR ligand genotyping might help to stratify future patients to immunotherapy treatment and avoid toxic side effects in patients who might not benefit from immunotherapy.

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