Huang Julian, Fogg Mark, Wirth Lori J, Daley Heather, Ritz Jerome, Posner Marshall R, Wang Fred C, Lorch Jochen H
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Infectious Diseases Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Cancer. 2017 Jul 15;123(14):2642-2650. doi: 10.1002/cncr.30541. Epub 2017 Feb 21.
Early-stage and intermediate-stage nasopharyngeal cancer (NPC) generally carry a good prognosis, but for patients with recurrent, metastatic disease, options are limited. In the current study, the authors present a phase 1/2 study to evaluate the efficacy of Epstein-Barr virus (EBV)-stimulated cytotoxic T-lymphocyte (EBV-CTL) immunotherapy in this patient population.
Screening for patients with active, recurrent, metastatic EBV-associated NPC began in February 2007, and the study was closed to accrual in January 2012. After informed consent was obtained, patients had their blood drawn to initiate manufacturing of the EBV-CTL product. During product manufacturing, patients were placed on interim standard-of-care chemotherapy, and only after disease progression on the interim chemotherapy did patients receive investigational immunotherapy. Patients were restaged every 2 months until disease progression and then followed for survival.
A total of 28 patients were enrolled, and 21 patients were treated. There was 1 complete response achieved, and at the time of last follow-up, the patient had been in remission for >8 years since treatment. The median progression-free survival was 2.2 months, and the median overall survival was 16.7 months. Two other patients, after failing EBV-CTL immunotherapy, unexpectedly demonstrated strong responses to the chemotherapy regimens they had previously failed. Patient EBV viral load and EBV-CTL specificity for tumor-associated viral antigens did not appear to correlate with clinical response.
A durable response was observed with EBV-CTL immunotherapy, but the overall response rate for patients with recurrent, metastatic NPC was low. Further research is necessary to increase the efficacy of EBV-specific immunotherapy in patients with incurable NPC, and to characterize mechanisms for refacilitation to chemotherapy. Cancer 2017;123:2642-50. © 2017 American Cancer Society.
早期和中期鼻咽癌（NPC）通常预后良好，但对于复发、转移性疾病患者，治疗选择有限。在本项研究中，作者开展了一项1/2期研究，以评估爱泼斯坦-巴尔病毒（EBV）刺激的细胞毒性T淋巴细胞（EBV-CTL）免疫疗法在该患者群体中的疗效。
2007年2月开始筛选活动性、复发性、转移性EBV相关NPC患者，该研究于2012年1月停止入组。获得知情同意后，采集患者血液以启动EBV-CTL产品的制备。在产品制备期间，患者接受中期标准护理化疗，只有在中期化疗出现疾病进展后，患者才接受研究性免疫疗法。每2个月对患者进行重新分期，直至疾病进展，然后进行生存随访。
共入组28例患者，21例患者接受了治疗。有1例患者获得完全缓解，在最后一次随访时，该患者自治疗后已缓解超过8年。无进展生存期的中位数为2.2个月，总生存期的中位数为16.7个月。另外两名患者在EBV-CTL免疫疗法失败后，意外地对他们之前失败的化疗方案表现出强烈反应。患者EBV病毒载量以及EBV-CTL对肿瘤相关病毒抗原的特异性似乎与临床反应无关。
观察到EBV-CTL免疫疗法有持久反应，但复发、转移性NPC患者的总体反应率较低。有必要进一步研究，以提高EBV特异性免疫疗法对无法治愈的NPC患者的疗效，并明确对化疗重新敏感的机制。《癌症》2017年；123：2642 - 2650。©2017美国癌症协会
