Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group

Amy K. Erbe; Wei Wang; Lakeesha Carmichael; Kyung Mann Kim; Eneida A. Mendoņca; Yiqiang Song; Dustin Hess; Patrick K. Reville; Wendy B. London; Arlene Naranjo; Jacquelyn A. Hank; Mitchell B. Diccianni; Ralph A. Reisfeld; Stephen D. Gillies; Katherine K. Matthay; Susan L. Cohn; Michael D. Hogarty; John M. Maris; Julie R. Park; M. Fevzi Ozkaynak; Andrew L. Gilman; Alice L. Yu; Paul M. Sondel

doi:10.1158/1078-0432.CCR-17-1767

Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group

Amy K. Erbe, Wei Wang, Lakeesha Carmichael, Kyung Mann Kim, Eneida A. Mendoņca, Yiqiang Song, Dustin Hess, Patrick K. Reville, Wendy B. London, Arlene Naranjo, Jacquelyn A. Hank, Mitchell B. Diccianni, Ralph A. Reisfeld, Stephen D. Gillies, Katherine K. Matthay, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Julie R. Park, M. Fevzi OzkaynakAndrew L. Gilman, Alice L. Yu, Paul M. Sondel

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial. Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIRligand genotypes. Results: In this trial, patients with the "all KIR-ligands present" genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone. Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIRligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.

Original language	English (US)
Pages (from-to)	189-196
Number of pages	8
Journal	Clinical Cancer Research
Volume	24
Issue number	1
DOIs	https://doi.org/10.1158/1078-0432.CCR-17-1767
State	Published - Jan 1 2018
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1158/1078-0432.CCR-17-1767

Cite this

Erbe, A. K., Wang, W., Carmichael, L., Kim, K. M., Mendoņca, E. A., Song, Y., Hess, D., Reville, P. K., London, W. B., Naranjo, A., Hank, J. A., Diccianni, M. B., Reisfeld, R. A., Gillies, S. D., Matthay, K. K., Cohn, S. L., Hogarty, M. D., Maris, J. M., Park, J. R., ... Sondel, P. M. (2018). Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group. Clinical Cancer Research, 24(1), 189-196. https://doi.org/10.1158/1078-0432.CCR-17-1767

Erbe, AK, Wang, W, Carmichael, L, Kim, KM, Mendoņca, EA, Song, Y, Hess, D, Reville, PK, London, WB, Naranjo, A, Hank, JA, Diccianni, MB, Reisfeld, RA, Gillies, SD, Matthay, KK, Cohn, SL, Hogarty, MD, Maris, JM, Park, JR, Ozkaynak, MF, Gilman, AL, Yu, AL & Sondel, PM 2018, 'Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group', Clinical Cancer Research, vol. 24, no. 1, pp. 189-196. https://doi.org/10.1158/1078-0432.CCR-17-1767

@article{9d7894483bba400a83d0d0a52c9833e6,

title = "Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group",

abstract = "Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial. Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIRligand genotypes. Results: In this trial, patients with the {"}all KIR-ligands present{"} genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone. Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIRligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.",

author = "Erbe, {Amy K.} and Wei Wang and Lakeesha Carmichael and Kim, {Kyung Mann} and Mendoņca, {Eneida A.} and Yiqiang Song and Dustin Hess and Reville, {Patrick K.} and London, {Wendy B.} and Arlene Naranjo and Hank, {Jacquelyn A.} and Diccianni, {Mitchell B.} and Reisfeld, {Ralph A.} and Gillies, {Stephen D.} and Matthay, {Katherine K.} and Cohn, {Susan L.} and Hogarty, {Michael D.} and Maris, {John M.} and Park, {Julie R.} and Ozkaynak, {M. Fevzi} and Gilman, {Andrew L.} and Yu, {Alice L.} and Sondel, {Paul M.}",

note = "Publisher Copyright: {\textcopyright} 2017 AACR.",

year = "2018",

month = jan,

day = "1",

doi = "10.1158/1078-0432.CCR-17-1767",

language = "English (US)",

volume = "24",

pages = "189--196",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "1",

}

TY - JOUR

T1 - Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy

T2 - A report from the children's oncology group

AU - Erbe, Amy K.

AU - Wang, Wei

AU - Carmichael, Lakeesha

AU - Kim, Kyung Mann

AU - Mendoņca, Eneida A.

AU - Song, Yiqiang

AU - Hess, Dustin

AU - Reville, Patrick K.

AU - London, Wendy B.

AU - Naranjo, Arlene

AU - Hank, Jacquelyn A.

AU - Diccianni, Mitchell B.

AU - Reisfeld, Ralph A.

AU - Gillies, Stephen D.

AU - Matthay, Katherine K.

AU - Cohn, Susan L.

AU - Hogarty, Michael D.

AU - Maris, John M.

AU - Park, Julie R.

AU - Ozkaynak, M. Fevzi

AU - Gilman, Andrew L.

AU - Yu, Alice L.

AU - Sondel, Paul M.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial. Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIRligand genotypes. Results: In this trial, patients with the "all KIR-ligands present" genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone. Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIRligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.

AB - Purpose: In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via natural killer (NK) cells. Killer immunoglobulin-like receptors (KIR) on NK cells and their interactions with KIR-ligands can influence NK cell function. We investigated whether KIR/KIR-ligand genotypes were associated with EFS or OS in this trial. Experimental Design: We genotyped patients from COG study ANBL0032 and evaluated the effect of KIR/KIR-ligand genotypes on clinical outcomes. Cox regression models and log-rank tests were used to evaluate associations of EFS and OS with KIR/KIRligand genotypes. Results: In this trial, patients with the "all KIR-ligands present" genotype as well as patients with inhibitory KIR2DL2 with its ligand (HLA-C1) together with inhibitory KIR3DL1 with its ligand (HLA-Bw4) were associated with improved outcome if they received immunotherapy. In contrast, for patients with the complementary KIR/KIR-ligand genotypes, clinical outcome was not significantly different for patients who received immunotherapy versus those receiving isotretinoin alone. Conclusions: These data show that administration of immunotherapy is associated with improved outcome for neuroblastoma patients with certain KIR/KIR-ligand genotypes, although this was not seen for patients with other KIR/KIR-ligand genotypes. Further investigation of KIR/KIRligand genotypes may clarify their role in cancer immunotherapy and may enable KIR/KIR-ligand genotyping to be used prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.

UR - http://www.scopus.com/inward/record.url?scp=85040058381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040058381&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-17-1767

DO - 10.1158/1078-0432.CCR-17-1767

M3 - Article

C2 - 28972044

AN - SCOPUS:85040058381

SN - 1078-0432

VL - 24

SP - 189

EP - 196

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 1

ER -

Neuroblastoma patients' KIR and KIR-ligand genotypes influence clinical outcome for dinutuximab-based immunotherapy: A report from the children's oncology group

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this