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

Autor:	Yu AL; University of California in San Diego, San Diego, California. a1yu@ucsd.edu pmsondel@humonc.wisc.edu.; Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan., Gilman AL; PRA Health Services, Raleigh, North Carolina., Ozkaynak MF; New York Medical College, Valhalla, New York., Naranjo A; Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida., Diccianni MB; University of California in San Diego, San Diego, California., Gan J; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin., Hank JA; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin., Batova A; University of California in San Diego, San Diego, California., London WB; Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Harvard Medical School, Boston, Massachusetts., Tenney SC; Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, Florida., Smith M; National Cancer Institute, Bethesda, Maryland., Shulkin BL; Saint Jude Children's Research Hospital, Memphis, Tennessee., Parisi M; Seattle Children's Hospital and University of Washington School of Medicine, Seattle, Washington., Matthay KK; University of California School of Medicine and UCSF Children's Hospital, San Francisco, California., Cohn SL; University of Chicago, Chicago, Illinois., Maris JM; Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania., Bagatell R; Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania., Park JR; Seattle Children's Hospital and University of Washington School of Medicine, Seattle, Washington., Sondel PM; University of Wisconsin Carbone Cancer Center, Madison, Wisconsin. a1yu@ucsd.edu pmsondel@humonc.wisc.edu.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Apr 15; Vol. 27 (8), pp. 2179-2189. Date of Electronic Publication: 2021 Jan 27.
DOI:	10.1158/1078-0432.CCR-20-3909
Abstrakt:	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. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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