PRELIMINARY RESULTS OF GEMCITABINE, ETOPOSIDE, MITOXANTRONE HYDROCHLORIDE LIPOSOME AND DEXAMETHASONE REGIMEN FOR NEWLY DIAGNOSED EARLY NUAT OR ADVANCED STAGE ENKTL

Abstract

Introduction: Extra-nodal NK/T-cell lymphoma (ENKTL) is an aggressive disease common in Asia but rare in the West. More than two-thirds of persons have stage I/II disease of the upper aero-digestive tract (UAT), which have relatively superior prognosis. However, patient of early non-UAT (NUAT) or advanced stage show an aggressive clinical course with extremely poor prognosis and low survival rates. Mitoxantrone hydrochloride liposome has reported to have efficacy in relapsed/ refractory (R/R) ENKTL in a phase II clinical trial. Furthermore, patient of early NUAT or advanced stage always have hemophagocytic lymphohistiocytosis (HLH) at diagnosis. Therefore, etoposide and high dose dexamethasone were also important for these patients. Based on these facts, this study evaluates the efficacy and safety of the regimen of gemcitabine, etoposide, mitoxantrone hydrochloride liposome, and dexamethasone (P-GEMD) in patients of newly diagnosed early NUAT or advanced stage ENKTL. Methods: Patients diagnosed as ENKTL in early NUAT and advanced stage form 18‒80 years with ECOG of 0‒2 were eligible for enrollment. We planned a maximum of 6 cycles of P-GEMD regimens for patients. The P-GEMD regimen was administered intravenously every 3 weeks until disease progression (PD) or unacceptable toxicity as follows (Figure 1A): pegaspargase at 2500 IU/m2 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. The primary endpoint is complete response rate (CRR). The second endpoint are overall response rate (ORR), duration of response (DOR) and 1-year overall survival (OS) and progression-free survival (PFS). Results: Five patients were preliminarily planned for P-GEMD regimens. Median age was 51y (range 44‒60 y). All the five patients were advanced stage with B symptoms. The median PINK and PINK-E score was 2 (range 2‒4) and 3 (range 3‒4), respectively. Two patients experienced HLH at diagnosis. All the five patients completed the induction of P-GEMD regimens with the median cycles of 6 (range 3‒6). Only 1 patient experienced PD while the other 4 patients were evaluated as CR by PET-CT. Therefore, the CRR is 80% (Figure 1B). Furthermore, the 4 patients with CR evaluated by PET-CT were all negatively for minimal residual disease (circulating tumor DNA) checked by next generation sequencing (NGS) while the ctDNA burden of patient with PD was positive (Figure 1C-G). There were 30 adverse events (AEs) recorded, of which 86.7% were grade 1 or 2. Hypo-fibrinogenemia, hypo-albuminemia and asparate transaminase increase were the most common grade 3 or 4 AEs (Figure 1H). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Chemotherapy, Combination Therapies No conflicts of interests pertinent to the abstract.