Study Identifies Patients Who Benefit Most From Dinutuximab-based Immunotherapy

Paul Sondel, MD, PhD
Paul Sondel, MD, PhD
Wei Wang
Wei Wang
Amy K. Erbe-Gurel, PhD
Amy K. Erbe-Gurel, PhD

Using data from a randomized phase III clinical trial of neuroblastoma patients (treated with or without immunotherapy) performed by the Children’s Oncology Group, researchers from the University of Wisconsin School of Medicine and Public Health found that a subset of patients, identified by the presence of a certain set of genes, were more likely to benefit from the immunotherapy than those patients that did not have that set of genes.

The trial, which involved 226 patients, was led by the Children’s Oncology Group, a coalition of research institutions across the country. The organization previously reported that the group of high-risk neuroblastoma patients that were treated with the immunotherapy regimen [dinutuximab (Unituxin), aldesleukin and sargramostim] in combination with isotretinoin had significantly improved event-free and overall survival as compared to patients that received isotretinoin alone.

Researchers at the University of Wisconsin-Madison, Amy Erbe and Wei Wang, in the lab of Dr. Paul Sondel, led an effort to determine if individual genetic differences could influence clinical response to this immunotherapy.  Dinutuximab is a monoclonal antibody that can kill cancer cells by activating natural killer (NK) cells. Killer Immunoglobulin-like Receptors (KIRs), a family of certain proteins expressed by NK cells, have different genetic patterns that can influence how well the NK cells use dinituximab to kill cancer cells. Dr. Sondel’s research team received DNA from 174 of the 226 patients that were enrolled in the clinical trial, and assessed how the pattern of KIR genes in each patient influenced outcome.

The study found that patients with a certain combination of four genes – (genes that inhibit NK cells) had improved outcomes with the immunotherapy. In contrast those patients without that combination of those four genes did not seem to have improvement from the immunotherapy.

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