CAPA induction followed by sequential radiotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma: a multicentre, single-arm, phase 2 trial

Background: Combined asparaginase-based chemoradiotherapy for early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is effective but often causes significant hematological toxicity and infection, compromising treatment delivery. We evaluated a chemotherapy-sparing induction regimen of camrelizumab, low-dose apatinib, and pegaspargase (CAPA) followed by sequential radiotherapy. Methods: In this multicentre, single-arm, phase 2 trial, adults with biopsy-confirmed nasal or upper aerodigestive tract NKTCL (WHO 2016; Lugano stage IE/IIE) received four 21-day cycles of CAPA followed by intensity-modulated radiotherapy (50–56 Gy). The primary endpoint was complete response (CR) at week 24 by Lugano 2014. Safety was assessed in all treated patients. Exploratory analyses examined interim response and plasma EBV DNA dynamics. Trial registration: NCT04366128. Findings: Between June 2020 and Oct 2022, 61 patients received CAPA; 54 (88·5%) had an evaluable week-24 assessment. Week-24 CR was 88.9% (48/54; 95% CI 77·4–95·8) and overall response was 92.6% (95% CI 82·1–97·9). At median follow-up 42.2 months (IQR 34·7–46·1), 2-year progression-free survival was 83·3% (95% CI 70·4–91·0) and overall survival was 88.9% (76·9–94·9). Grade 3–4 treatment-related adverse events occurred in 29 (47·5%) patients, mainly hypertriglyceridaemia (19·7%) and hypertension (11·5%); grade 3–4 neutropenia occurred in two (3·3%) and anaemia in one (1·6%), with no treatment-related deaths. Week-12 non-response (SD/PD) and lack of plasma EBV DNA clearance by week 24 (EBV-notclear) were associated with inferior survival. Interpretation: CAPA followed by sequential radiotherapy achieved high CR and durable disease control with minimal severe haematological toxicity in early-stage NKTCL, supporting comparative evaluation and prospective integration of PET-based response assessment and plasma EBV-DNA monitoring.