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Key role for myeloid cells: Phase II results of anti‐G D2 antibody 3F8 plus granulocyte‐macrophage colony‐stimulating factor for chemoresistant osteomedullary neuroblastoma
Author(s) -
Cheung NaiKong V.,
Cheung Irene Y.,
Kramer Kim,
Modak Shakeel,
Kuk Deborah,
PanditTaskar Neeta,
Chamberlain Elizabeth,
Ostrovnaya Irina,
Kushner Brian H.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28851
Subject(s) - medicine , neuroblastoma , myeloid , antibody , bone marrow , phases of clinical research , oncology , immunology , clinical trial , cancer research , biology , cell culture , genetics
Anti‐G D2 murine antibody 3F8 plus subcutaneously (sc) administered granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was used against primary refractory neuroblastoma in metastatic osteomedullary sites. Large study size and long follow‐up allowed assessment of prognostic factors in a multivariate analysis not reported with other anti‐G D2 antibodies. In a phase II trial, 79 patients without prior progressive disease were treated for persistent osteomedullary neuroblastoma documented by histology and/or metaiodobenzyl‐guanidine (MIBG) scan. In the absence of human antimouse antibody, 3F8 + scGM‐CSF cycles were repeated up to 24 months. Minimal residual disease (MRD) in bone marrow was measured by quantitative reverse transcription‐polymerase chain reaction pre‐enrollment and post‐cycle #2, before initiation of 13‐ cis ‐retinoic acid. Study endpoints were: ( i ) progression‐free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously administered (iv) GM‐CSF (26 patients) and ( ii ) impact of MRD on PFS. Using all 105 patients from the two consecutive 3F8 + GM‐CSF trials, prognostic factors were analyzed by multivariate Cox regression model. Complete response rates to 3F8 + scGM‐CSF were 87% by histology and 38% by MIBG. Five‐year PFS was 24 ± 6%, which was significantly superior to 11 ± 7% with 3F8 + ivGM‐CSF ( p = 0.002). In the multivariate analysis, significantly better PFS was associated with R/R or H/R FCGR2A polymorphism, sc route of GM‐CSF and early MRD response. MYCN amplification was not prognostic. Complement consumption was similar with either route of GM‐CSF. Toxicities were manageable, allowing outpatient treatment. 3F8 + scGM‐CSF is highly active against chemoresistant osteomedullary neuroblastoma. MRD response may be an indicator of tumor sensitivity to anti‐G D2 immunotherapy. Correlative studies highlight the antineoplastic potency of myeloid effectors.