Key role for myeloid cells: phase II results of anti-G(D2) antibody 3F8 plus granulocyte-macrophage colony-stimulating factor for chemoresistant osteomedullary neuroblastoma.
Key role for myeloid cells: phase II results of anti-G(D2) antibody 3F8 plus granulocyte-macrophage colony-stimulating factor for chemoresistant osteomedullary neuroblastoma.
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DOI：
10.1002/ijc.28851
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发表时间：
2014-11-01
影响因子：
6.4
通讯作者：
Kushner BH
中科院分区：
文献类型：
--
作者：
Cheung NK;Cheung IY;Kramer K;Modak S;Kuk D;Pandit-Taskar N;Chamberlain E;Ostrovnaya I;Kushner BH
应用抗GD2鼠抗体3F8联合皮下注射粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗转移性骨髓质原发难治性神经母细胞瘤。较大的研究规模和较长的随访期允许在未报道其他抗GD2抗体的多变量分析中评估预后因素。在II期试验中，79名既往没有进展性疾病的患者接受了经组织学和/或间碘苯甲基胍(MIBG)扫描证实的持续性骨髓质神经母细胞瘤的治疗。在没有人抗鼠抗体的情况下，重复3F8+scGM-CSF周期长达24个月。用定量逆转录聚合酶链式反应检测骨髓微小残留病(MRD)，在登记前和周期2后，在13-顺式维甲酸开始之前。研究的终点是：1)与3F8加静脉给药(Iv)GM-CSF(26名患者)的前人试验相比，无进展生存期(PFS)，以及2)MRD对PFS的影响。对连续两次3F8+GM-CSF试验的105例患者的预后因素进行多因素Cox回归分析。3F8+scGM-CSF的完全缓解率组织学为87%，MIBG为38%。5年生存率为24%±6%，明显优于3F8+静脉注射GM-CSF组的11%±7%(P=0.002)。在多因素分析中，较好的PFS与R/R或H/R FCGR2A型、GM-CSF的sc途径和早期MRD反应相关。MYCN扩增不能预测预后。补体消耗与两种途径中的GM-CSF相似。毒性是可控的，允许门诊治疗。3F8+scGM-CSF对化疗耐药的骨髓质神经母细胞瘤具有很强的抗化疗活性。MRD反应可能是肿瘤对抗GD2免疫治疗敏感性的一个指标。相关研究强调了髓系效应物的抗肿瘤效力。
Anti-GD2 murine antibody 3F8 plus subcutaneously-administered (sc) 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-GD2 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 anti-mouse 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: 1) progression-free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously-administered (iv) GM-CSF (26 patients), and 2) 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-GD2 immunotherapy. Correlative studies highlight the anti-neoplastic potency of myeloid effectors.
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影响因子：
3.4
作者：
Dillman, Robert O.
通讯作者：
Dillman, Robert O.
影响因子：
45.3
作者：
Cheung, Nai-Kong V.;Cheung, Irene Y.;Modak, Shakeel
通讯作者：
Modak, Shakeel
影响因子：
45.3
作者：
BRODEUR, GM;PRITCHARD, J;VOUTE, PA
通讯作者：
VOUTE, PA
DOI：
10.1158/1078-0432.ccr-08-0541
发表时间：
2008-11-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cheung IY;Feng Y;Gerald W;Cheung NK
通讯作者：
Cheung NK
影响因子：
45.3
作者：
Cheung, Irene Y.;Hsu, Katharine;Cheung, Nai-Kong V.
通讯作者：
Cheung, Nai-Kong V.