PURPOSE: Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. PATIENTS AND METHODS: One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. RESULTS: At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). CONCLUSION: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.
PURPOSE: Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. PATIENTS AND METHODS: One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. RESULTS: At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). CONCLUSION: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.
Authors: Brian H Kushner; Irene Y Cheung; Kim Kramer; Shakeel Modak; Nai-Kong V Cheung Journal: Pediatr Blood Cancer Date: 2007-04 Impact factor: 3.167
Authors: Leonid S Metelitsa; Stephen D Gillies; Michael Super; Hiroyuki Shimada; C Patrick Reynolds; Robert C Seeger Journal: Blood Date: 2002-06-01 Impact factor: 22.113
Authors: Katherine K Matthay; Veronique Edeline; Jean Lumbroso; Marie Laure Tanguy; Bernard Asselain; Jean Michel Zucker; Dominique Valteau-Couanet; Olivier Hartmann; Jean Michon Journal: J Clin Oncol Date: 2003-07-01 Impact factor: 44.544
Authors: Brian H Kushner; Stephen S Roberts; Danielle N Friedman; Deborah Kuk; Irina Ostrovnaya; Shakeel Modak; Kim Kramer; Ellen M Basu; Nai-Kong V Cheung Journal: Cancer Date: 2015-02-27 Impact factor: 6.860
Authors: Nan Li; Haiying Fu; Stephen M Hewitt; Dimiter S Dimitrov; Mitchell Ho Journal: Proc Natl Acad Sci U S A Date: 2017-07-24 Impact factor: 11.205
Authors: Dana L Casey; Brian H Kushner; Nai-Kong V Cheung; Shakeel Modak; Ellen M Basu; Stephen S Roberts; Michael P LaQuaglia; Suzanne L Wolden Journal: Int J Radiat Oncol Biol Phys Date: 2019-02-11 Impact factor: 7.038
Authors: Brian H Kushner; Irene Y Cheung; Shakeel Modak; Kim Kramer; Govind Ragupathi; Nai-Kong V Cheung Journal: Clin Cancer Res Date: 2014-02-11 Impact factor: 12.531