Merchant Melinda S, Bernstein Donna, Amoako Martha, Baird Kristin, Fleisher Thomas A, Morre Michel, Steinberg Seth M, Sabatino Marianna, Stroncek Dave F, Venkatasan Aradhana M, Wood Bradford J, Wright Matthew, Zhang Hua, Mackall Crystal L
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH Clinical Center, Bethesda, Maryland.
Department of Laboratory Medicine, NIH Clinical Center, Bethesda, Maryland.
Clin Cancer Res. 2016 Jul 1;22(13):3182-91. doi: 10.1158/1078-0432.CCR-15-2550. Epub 2016 Jan 28.
Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.
Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).
Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.
Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182-91. ©2016 AACR.
转移性或复发性小儿肉瘤患者接受的细胞毒性治疗方案可诱导较高的缓解率，但会导致严重的淋巴细胞耗竭，最终很少有患者能长期存活。我们对转移性和复发性小儿肉瘤患者实施辅助免疫治疗，以改善治疗效果。
入组时通过单采术采集单核细胞，并通过经皮活检获取肿瘤裂解物。参与者接受标准抗肿瘤治疗，随后接受自体淋巴细胞、肿瘤裂解物/钥孔戚血蓝蛋白脉冲树突状细胞疫苗接种±重组人白细胞介素7。主要结局为毒性和疫苗反应。次要结局为免疫重建、无事件生存期和总生存期（OS）。
43例患者入组，29例接受免疫治疗。该方案耐受性良好。意向性分析显示5年总生存率为51%，根据组织学类型存在显著差异（尤因肉瘤/横纹肌肉瘤为63%，其他肉瘤为0%）以及对标准治疗的反应（无残留疾病者为74%，有残留疾病者为0%）。新诊断的转移性尤因肉瘤/横纹肌肉瘤患者的5年意向性分析总生存率为77%，高于该人群先前报道的生存率，也高于接受早期辅助免疫治疗方案的类似组所观察到的生存率（5年总生存率为25%）。62%的免疫治疗接受者检测到对自体肿瘤裂解物的T细胞反应，这些患者的生存率更高（有免疫反应者5年总生存率为73%，无免疫反应者为37%，P = 0.017）。通过CD4计数恢复来衡量的免疫重建在接受重组人白细胞介素7治疗的受试者中显著增强。
辅助免疫治疗可能改善转移性小儿肉瘤患者的生存率。《临床癌症研究》；22(13)；3182 - 91。©2016美国癌症研究协会。
