This prospective, multicenter study evaluates a response-adapted treatment strategy for previously untreated patients with early-stage extranodal NK/T-cell lymphoma of the upper aerodigestive tract.
All participants receive two cycles of GELAD induction chemotherapy, followed by early response assessment using positron emission tomography/computed tomography (PET/CT) and plasma Epstein-Barr virus (EBV) DNA. Subsequent treatment is determined by the early response.
Participants with complete metabolic response and negative EBV DNA enter PART A and are randomized 1:1 to standard-dose radiotherapy (50 Gy) or reduced-dose radiotherapy (40 Gy); both groups subsequently receive two additional cycles of GELAD. Participants with partial response and negative EBV DNA enter PART B and receive standard 50 Gy radiotherapy followed by two additional cycles of GELAD. Participants with stable disease, local or regional progressive disease that remains amenable to curative radiotherapy, or partial response with positive EBV DNA enter PART C and receive 50 Gy radiotherapy followed by response-adapted sintilimab consolidation.
The primary objective of PART A is to determine whether reduced-dose radiotherapy is noninferior to standard-dose radiotherapy with respect to the 24-month progression-free survival rate. The primary objective of PART C is to evaluate the 24-month progression-free survival rate with response-adapted sintilimab consolidation in patients with a high-risk early response.
Age 18 to 75 years, inclusive.
Histologically confirmed extranodal NK/T-cell lymphoma, nasal type, according to the 2022 World Health Organization classification.
Diagnosis confirmed by institutional or central pathological review. Tumor tissue must be adequate for morphological assessment, immunohistochemistry, and Epstein-Barr virus-encoded RNA in situ hybridization.
Lugano 2014 stage IE or IIE disease with a primary site in the upper aerodigestive tract, including but not limited to the nasal cavity, paranasal sinuses, nasopharynx, oropharynx, or oral cavity.
Diagnosis not meeting the 2022 World Health Organization criteria for extranodal NK/T-cell lymphoma or not confirmed after pathological review.
Lugano stage III or IV disease or distant organ involvement inconsistent with localized early-stage disease.
Primary disease outside the upper aerodigestive tract or predominantly systemic or widespread extranodal disease.
Previous lymphoma-directed chemotherapy, radiotherapy, immunotherapy, or other systemic antitumor treatment.