Long-term immune checkpoint inhibitor therapy in a patient with metastatic nasopharyngeal carcinoma: a case report

Abstract

Background: Immunotherapy has revolutionized cancer treatment. However, the duration of treatment and the timing of discontinuation are major concerns. Current pivotal trials predominantly advocate for a fixed two-year regimen of immune checkpoint inhibitors (ICIs), exemplified by pembrolizumab and toripalimab, as first-line therapy for patients with advanced malignancies. Alternatively, for specific ICIs, including nivolumab, camrelizumab, and tislelizumab, continuous administration until disease progression has emerged as a favored approach. Nevertheless, whether to discontinue treatment after two years remains intensely debated within the medical community, underscoring the need for further research to clarify optimal treatment durations.

Case presentation: In November 2018, a 44-year-old male presented with a persistent headache. Following a positive nasopharyngeal mucosal biopsy, he was diagnosed with non-keratinizing undifferentiated carcinoma of the nasopharynx cT4N2M0. An Epstein-Barr Virus (EBV) DNA load of 800 copies/mL was detected. The patient completed two cycles of induction chemotherapy with liposomal paclitaxel and nedaplatin, followed by platinum-based concurrent chemoradiotherapy, resulting in a progression-free survival (PFS) of 23.6 months. The EBV DNA load dropped significantly to 190 copies/mL. However, during a routine examination in January 2021, metastases in the lung and mediastinal lymph nodes were detected, and the EBV DNA load was measured at 2200 copies/mL. Consequently, surgical intervention was performed, followed by radiotherapy and two years of ICI treatment. Throughout the ICI maintenance period, the EBV DNA level remained consistently below the limit of detection. Remarkably, three months after treatment discontinuation, the patient exhibited a rebound in EBV DNA (1620 copies/mL). Nevertheless, imaging scans revealed no evidence of tumor progression. Following an ICI rechallenge, the patient's EBV DNA load returned to undetectable levels. The patient continues the ICI therapy and has thus far achieved a PFS of 41.6 months.

Conclusion: EBV DNA levels could serve as an informative marker to predict the necessity of therapy discontinuation during immunotherapy maintenance. Notably, a post-discontinuation ICI rechallenge can still yield favorable outcomes potentially accredited to immune memory.

Keywords: EBV DNA; immune checkpoint inhibitor; immunotherapy; therapy discontinuation; treatment duration.

Figure 1

The intensity-modulated radiotherapy plan for nasopharyngeal carcinoma demonstrates three distinct isodose distributions: the gross tumor volume (GTVnx) is encompassed by the 69.96 Gy isodose curve (slate blue), while the clinical target volumes CTV1 and CTV2 are covered by the 60.06 Gy (yellow) and 54.12 Gy (purple) isodose lines, respectively. Transverse (A) and coronal (B) sections illustrate the treatment plan in these planes.

Figure 2

Comparative imaging analysis delineates post-radiotherapy metastatic progression in thoracic regions. Post-treatment surveillance CT identified metastatic lesions in the pulmonary parenchyma (A) and mediastinal nodal stations (B). Dosimetric mapping demonstrates therapeutic coverage with the 60 Gy isodose contour (yellow) delineating the GTV, while the 54 Gy isodose (purple) demarcates the CTV in postoperative imaging series (C, D). Serial follow-up imaging shows sustained locoregional control (E, F), with no radiographic evidence of disease recurrence.

Figure 3

EBV DNA load demonstrates dynamic correlation with disease progression, serving both as a quantitative biomarker for therapeutic monitoring and a predictive indicator for treatment discontinuation criteria. The patient was found to have pulmonary and mediastinal lymph nodes metastases (A). A rebound in EBV DNA levels was recorded three months after discontinuing the treatment (B).