Introduction and Objectives:
Patients with advanced extranodal NK/T-cell lymphoma (ENKTL) or early-stage non-upper aero-digestive tract (NUAT) involvement face a poor prognosis and frequently develop hemophagocytic lymphohistiocytosis (HLH). This prospective, single-arm, multicenter, Phase II study aimed to evaluate the efficacy and safety of a novel regimen consisting of pegaspargase, gemcitabine, etoposide, mitoxantrone hydrochloride liposome, and dexamethasone (P-GEMD) in patients with newly diagnosed early-stage NUAT or advanced ENKTL.
Methods:
Patients received the P-GEMD regimen (pegaspargase at 3750 IU, d2; gemcitabine at 1000 mg/m2, d1; etoposide at 65 mg/m2, d2‒4; mitoxantrone hydrochloride liposome at 12 mg/m2, d1; dexamethasone at 40 mg/d, d1‒4) administered intravenously every 3 weeks until disease progression (PD), unacceptable toxicity or up to 6 cycles. The primary endpoint is complete response rate (CRR). The second endpoints are objective response rate (ORR), 1-year progression-free survival (PFS), 1-year overall survival (OS) and safety.
Results:
As of October 2025, 20 patients were enrolled, including 16 (80.0%) with advanced nasal-type ENKTL and 4 (20.0%) with NUAT-ENKTL. At the data cutoff, the best CRR was 80% (16/20), and the ORR was 90% (18/20). Patients with HLH achieved a CRR of 75% (3/4). With a median follow-up of 20.5 months, median PFS and OS were not reached. The 1-year PFS and OS rates were 69.2% and 78.8%, respectively. The most common grade 3–4 treatment-related adverse events (TRAEs) with an incidence ≥20% included leukopenia (70.0%), anemia (55.0%), neutropenia (50.0%), thrombocytopenia (35.0%), Lymphocytopenia (25.0%), and hypocalcemia (20.0%).
Conclusion:
The P-GEMD regimen demonstrated encouraging preliminary antitumor activity and manageable toxicity as a first-line treatment for early-stage NUAT or advanced ENKTL.
