e-Article
A Phase II Trial of Hu14.18K322A in Combination with Induction Chemotherapy in Children with Newly Diagnosed High-Risk Neuroblastoma
Document Type
article
Author
Furman, Wayne L; Federico, Sara M; McCarville, Mary Beth; Shulkin, Barry L; Davidoff, Andrew M; Krasin, Matthew J; Sahr, Natasha; Sykes, April; Wu, Jianrong; Brennan, Rachel C; Bishop, Michael William; Helmig, Sara; Stewart, Elizabeth; Navid, Fariba; Triplett, Brandon; Santana, Victor M; Bahrami, Armita; Anthony, Gwendolyn; Yu, Alice L; Hank, Jacquelyn; Gillies, Stephen D; Sondel, Paul M; Leung, Wing H; Pappo, Alberto S
Source
Clinical Cancer Research. 25(21)
Subject
Language
Abstract
PurposeWe sought to evaluate whether combining a humanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma.Patients and methodsWe conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoin were then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123I-metaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction.ResultsForty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3).ConclusionsAdding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.