期刊
CLINICAL CANCER RESEARCH
卷 27, 期 8, 页码 2179-2189出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-20-3909
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类别
资金
- NIH/NCI [U10CA180899, U10CA98543, U10CA180886]
- St. Baldrick's Foundation
- Alex's Lemonade Stand Foundation
- Padres Foundation
- Lou Bridgeman Memorial Fund [R35 CA197078]
- Midwest Athletes against Childhood Cancer
- NCI [R35 CA220500]
The study showed that immuotherapy with dinutuximab improved outcomes for high-risk neuroblastoma patients. Although early termination for efficacy resulted in a smaller sample size, clinically significant long-term survival differences were observed.
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 tomeeting 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. Fc gamma 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. Fc gamma 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.
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