NYMC Faculty Publications

Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group

Ami V. Desai, University of Chicago, Chicago, IL.
Andrew L. Gilman, ICON plc, Raleigh, NC.
Mehmet Fevzi Ozkaynak, Maria Fareri Children's Hospital Westchester Medical Center, New York Medical College, Valhalla, NY.
Arlene Naranjo, Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL.
Wendy B. London, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA.
Sheena C. Tenney, Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL.
Mitchell Diccianni, University of California in San Diego, San Diego, CA.
Jacquelyn A. Hank, University of Wisconsin Carbone Cancer Center, Madison, WI.
Marguerite T. Parisi, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA.
Barry L. Shulkin, St Jude Children's Research Hospital, Memphis, TN.
Malcolm Smith, Clinical Investigations Branch, National Cancer Institute, Bethesda, MD.
Jeffrey A. Moscow, Investigational Drug Branch, National Cancer Institute, Bethesda, MD.
Hiroyuki Shimada, Stanford University Medical Center, Stanford, CA.
Katherine K. Matthay, UCSF Benioff Children's Hospital, San Francisco, CA.
Susan L. Cohn, University of Chicago, Chicago, IL.
John M. Maris, Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA.
Rochelle Bagatell, Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA.
Paul M. Sondel, University of Wisconsin Carbone Cancer Center, Madison, WI.
Julie R. Park, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA.
Alice L. Yu, University of California in San Diego, San Diego, CA.

Author Type(s)

Faculty

Journal Title

Journal of Clinical Oncology

First Page

4107

Last Page

4118

Document Type

Article

Publication Date

12-10-2022

Department

Pediatrics

Abstract

PURPOSE: Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed. PATIENTS AND METHODS: Patients with a pre-autologous stem cell transplant (ASCT) response (excluding bone marrow) of partial response or better were eligible. Demographics, stage, tumor biology, pre-ASCT response, and adverse events were summarized using descriptive statistics. Event-free survival (EFS) and overall survival (OS) from time of enrollment (up to day +200 from last ASCT) were evaluated. RESULTS: From 2009 to 2015, 1,183 patients were treated. Five-year EFS and OS for the entire cohort were 61.1 ± 1.9% and 71.9 ± 1.7%, respectively. For patients ≥ 18 months old at diagnosis with International Neuroblastoma Staging System stage 4 disease (n = 662) 5-year EFS and OS were 57.0 ± 2.4% and 70.9 ± 2.2%, respectively. EFS was superior for patients with complete response/very good partial response pre-ASCT compared with those with PR (5-year EFS: 64.2 ± 2.2% 55.4 ± 3.2%, = .0133); however, OS was not significantly different. Allergic reactions, capillary leak, fever, and hypotension were more frequent during interleukin-2-containing cycles than granulocyte-macrophage colony-stimulating factor-containing cycles ( < .0001). EFS was superior in patients with higher peak dinutuximab levels during cycle 1 ( = .034) and those with a high affinity FCGR3A genotype ( = .0418). Human antichimeric antibody status did not correlate with survival. CONCLUSION: Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. EFS was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior EFS. These may be predictive biomarkers for dinutuximab therapy.

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