Long lasting responses to adoptive T-cell therapy in relapsed EBV-related nasopharyngeal carcinoma

Background: Epstein-Barr virus (EBV)-related Nasopharyngeal carcinoma (NPC) is a highly chemo-radiosensitive cancer. However, when relapsing without surgical or reirradiation options, NPC carries a dismal prognosis; survival >2 years being reported in 7-14% metastatic pts (1,2). We have previously achieved disease control using autologous EBV-specific cytotoxic T lymphocytes (CTL) in refractory/relapsed pts following conventional treatments (3). The aim of the present study was to evaluate outcomes in pts receiving T-cell therapy after first line chemotherapy (CT) for recurrent disease. Methods: Sixteen patients (13 males, median age 41 yrs) with metastatic (n = 12; 7/12 with visceral metastasis, and 5/12 with bone and nodes lesions) or locally recurrent (n = 4) NPC received 2 administrations of EBV-specific CTL at a total cell dose/infusion of 1.5-3 x 108, following completion of first line CT. The best response after first-line CT had been progressive disease (PD) in 4 pts, stable disease (SD) in 3, partial response (PR) in 5 and complete response (CR) in 4. Results: No severe adverse events were recorded, following CTL therapy. Among patients in CR after first-line CT, 3 remain in CR at 58, 76 and 77+ months, while one patient relapsed, but attained a long-lasting CR after treatment with 2nd-line CT. In the 12 patients treated with persistent disease (PR, SD, PD), the best response observed after CTL therapy, in some cases (3/12) associated with 1subsequent line of CT or radiotherapy, was PD in 8 patients, and CR (range 39-78+ months) in 4. At a median follow-up of 64 months, 8/16 patients are alive with no evidence of disease. Among the factors associated with positive outcome are response to first-line CT, and metastatic disease with limited tumor burden. Conclusions: EBV-specific CTL therapy administered following first line CT for recurrent NPC, is safe and associated with remarkable clinical benefit in some patients, including long-lasting CR. Legal entity responsible for the study: Fondazione IRCCS Policlinico San Matteo Pavia. Funding: Fondazione IRCCS Policlinico San Matteo, Ricerca Corrente RCR. Disclosure: All authors have declared no conflicts of interest.