title: Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma.
abstract: The outcomes for patients with metastatic or locally recurrent Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) remain poor. Adoptive immunotherapy with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) has proven clinical efficacy, but it has never been evaluated in the first-line treatment setting in combination with chemotherapy. To evaluate the safety and efficacy of a chemotherapy in combination with adoptive EBV-CTL transfer, we conducted a phase 2 clinical trial consisting of four cycles of gemcitabine and carboplatin (GC) followed by up to six doses of EBV-CTL. Thirty-eight patients were enrolled, and 35 received GC and EBV-CTL. GC-CTL therapy resulted in a response rate of 71.4% with 3 complete responses and 22 partial responses. With a median follow up of 29.9 months, the 2-year and 3-year overall survival (OS) rate was 62.9 and 37.1%, respectively. Five patients did not require further chemotherapy for more than 34 months since initiation of CTL. Infusion of CTL products containing T cells specific for LMP2 positively correlated with OS (hazard ratio: 0.35; 95% confidence interval: 0.14-0.84; P = 0.014). Our study achieved one of the best survival outcomes in patients with advanced NPC, setting the stage for a future randomized study of chemotherapy with and without EBV-CTL.
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Whay-Kuang
authors.initials: WK
authors.lastname: Chia
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Marissa
authors.initials: M
authors.lastname: Teo
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Who-Whong
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Soo-Fan
authors.initials: SF
authors.lastname: Ang
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wai-Meng
authors.initials: WM
authors.lastname: Tai
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Chit-Lai
authors.initials: CL
authors.lastname: Chee
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Wan-Teck
authors.initials: WT
authors.lastname: Lim
authors.affiliation: Division of Clinical Trials and Epidemiological Research, National Cancer Centre, Singapore.
authors.forename: Sze-Huey
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Division of Clinical Trials and Epidemiological Research, National Cancer Centre, Singapore.
authors.forename: Whee-Sze
authors.initials: WS
authors.lastname: Ong
authors.affiliation: Duke-NUS Graduate Medical School, Singapore.
authors.forename: Yin-Bun
authors.initials: YB
authors.lastname: Cheung
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: John E
authors.initials: JE
authors.lastname: Connolly
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Han-Chong
authors.initials: HC
authors.lastname: Toh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins