A Comprehensive Safety Trial of Chimeric Antibody 14.18 With GM-CSF, IL-2, and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy: Children’s Oncology Group Study ANBL0931
Year: 2018
Type: article
Abstract: Purpose: A phase 3 randomized study (COG ANBL0032) demonstrated significantly improved outcome by adding immunotherapy with ch14.18 antibody to isotretinoin as post-consolidation therapy for high-risk neuroblastoma (NB). This study, ANBL0931, was designed to collect FDA-required safety/toxicity data to support FDA registration of ch14.18. Experimental design: Newly diagnosed high-risk NB patients who achieved at least a partial response to induction therapy and received myeloablative consolidation with stem cell rescue were enrolled to receive six courses of isotretinoin with five concomitant cycles of ch14.18 combined with GM-CSF or IL2. Ch14.18 infusion time was 10-20 h per dose. Blood was collected for cytokine analysis and its association with toxicities and outcome. Results: Of 105 patients enrolled, five patients developed protocol-defined unacceptable toxicities. The most common grade ≥ 3 non-hematologic toxicities of immunotherapy for cycles 1-5, respectively, were neuropathic pain (41, 28, 22, 31, 24%), hypotension (10, 17, 4, 14, 8%), allergic reactions (ARs) (3, 10, 5, 7, 2%), capillary leak syndrome (1, 4, 0, 2, 0%), and fever (21, 59, 6, 32, 5%). The 3-year event-free survival and overall survival were 67.6 ± 4.8% and 79.1 ± 4.2%, respectively. AR during course 1 was associated with elevated serum levels of IL-1Ra and IFNγ, while severe hypotension during this course was associated with low IL5 and nitrate. Higher pretreatment CXCL9 level was associated with poorer event-free survival (EFS). Conclusion: This study has confirmed the significant, but manageable treatment-related toxicities of this immunotherapy and identified possible cytokine biomarkers associated with select toxicities and outcome. EFS and OS appear similar to that previously reported on ANBL0032.
Source: Frontiers in Immunology
Institutions: New York Medical College, Levine Children's Hospital, Boston Children's Hospital, Harvard University, Dana-Farber Cancer Institute, University of Florida, University of California San Diego, Moores Cancer Center, National Institutes of Health, National Cancer Institute, University of Southern California, Children's Hospital of Los Angeles, Texas Tech University Health Sciences Center, United Therapeutics (United States), St. Jude Children's Research Hospital, Seattle Children's Hospital, University of Washington, Children's Hospital of Philadelphia, University of Wisconsin–Madison, University of Wisconsin Carbone Cancer Center, Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: U.S. Department of Defense, Alex's Lemonade Stand Foundation for Childhood Cancer, St. Baldrick's Foundation, Children's Hospital of Philadelphia, Vanderbilt University, Cincinnati Children's Hospital Medical Center, St. Jude Children's Research Hospital, University of Texas Southwestern Medical Center, Loma Linda University, Children's Hospitals and Clinics of Minnesota, Children's Healthcare of Atlanta, National Institutes of Health, University of California, San Francisco, National Cancer Institute, School of Medicine, University of California, San Francisco
OpenAlex ID: W2805565362