A Phase 2 Multicenter Study of Pegaspargase in Combination with Gemcitabine, Etoposide, Mitoxantrone Hydrochloride Liposome, and Dexamethasone (P-GEMD) for Newly Diagnosed Early Non-Upper Aero-Digestive Tract or Advanced Stage Extranodal NK/T Cell Lymphom

Introduction: ENKTL is an aggressive disease and patients with early non upper aero digestive tract (NUAT) or advanced stage disease often exhibit an aggressive clinical course. Mitoxantrone hydrochloride liposome has demonstrated efficacy in relapsed/refractory ENKTL in a phase II clinical trial. Methods: 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) was administered intravenously every 3 weeks until disease progression or unacceptable toxicity or up to 6 cycles of planned therapy. The primary endpoint is CR rate. Objectives: This study aims to evaluate the efficacy and safety of a novel regimen consisting of pegaspargase, gemcitabine, etoposide, mitoxantrone hydrochloride liposome, and dexamethasone (P GEMD) which was modified in our previous PEMD regimen (Blood Cancer Journal, 2017) in newly diagnosed early NUAT or advanced stage ENKTL patients (NCT05774028). Results: As of December 2024, the study had finished the enrollment (20 patients) including 16 (80.0%) patients of advanced stage nasal type ENKTL and 4 (20.0%) of NUAT ENKTL. The median age was 37.5 years. 18 (90.0%) patients completed the induction of P GEMD regimen. At the data cutoff, the best CR rate was 77.8% (14/18) and ORR was 88.9% (16/18). With median follow up of 12.1 months, median PFS and OS are not reached. The grade ≥3 reatment related adverse events with an incidence ≥10% were hematological toxicity, hypocalcemia (20.0%) and hyponatremia (15.0%). Conclusion: P‐GEMD regimen has shown promising efficacy with manageable toxicities as a front‐line treatment.