Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.

Abstract

PURPOSE:

Previously our randomized phase III trial demonstrated that immunotherapy including dinutuximab, a chimeric anti-GD2 mAb, GM-CSF, and IL2 improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers.

PATIENTS AND METHODS:

Patients recieved six cycles of isotretinoin with or without five cycles of immunotherapy which consists of dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of dinutuximab, soluble IL2 receptor (sIL2R), and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcγ receptor 2A and 3A genotypes were determined by PCR and direct sequencing.

RESULTS:

For 226 eligible randomized patients, 5-year EFS was 56.6 ± 4.7% for patients randomized to immunotherapy (n = 114) versus 46.1 ± 5.1% for those randomized to isotretinoin only (n = 112; P = 0.042). Five-year overall survival (OS) was 73.2 ± 4.2% versus 56.6 ± 5.1% for immunotherapy and isotretinoin only patients, respectively (P = 0.045). Thirteen of 122 patients receiving dinutuximab developed HACA. Plasma levels of dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcγ receptor 2A and 3A genotypes did not correlate with EFS/OS.

CONCLUSIONS:

Immunotherapy with dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

• Authors: Alice L Yu, Andrew L Gilman, M Fevzi Ozkaynak, Arlene Naranjo, Mitchell B Diccianni, Jacek Gan, Jacquelyn A Hank, Ayse Batova, Wendy B London, Sheena C Tenney, Malcolm Smith, Barry L Shulkin, Marguerite Parisi, Katherine K Matthay, Susan L Cohn, John M Maris, Rochelle Bagatell, Julie R Park, Paul M Sondel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 8 Pg. 2179-2189 (04 15 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33504555 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• IL2 protein, human
• Interleukin-2
• Recombinant Proteins
• dinutuximab
• Isotretinoin

Topics

• Adolescent
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Follow-Up Studies
• Humans
• Infant
• Interleukin-2 (administration & dosage, adverse effects)
• Isotretinoin (administration & dosage, adverse effects)
• Male
• Neuroblastoma (drug therapy, mortality)
• Progression-Free Survival
• Recombinant Proteins (administration & dosage, adverse effects)