A MULTI‐CENTER STUDY OF GLIDE CHEMOTHERAPY CONSOLIDATED WITH AUTOLOGOUS STEM CELL TRANSPLANTATION FOR NEWLY DIAGNOSED STAGE IV AND RELAPSED EXTRANODAL NATURAL KILLER/T‐CELL LYMPHOMA PATIENTS

Abstract

Background: The prognosis of advanced-stage and relapsed extranodal NK/T cell lymphoma(ENKTL) is poor, with long term survival rate of 30%. Our previous study of GLIDE (gemcitabine, L-asparaginase, ifosfamide, dexamethasone and etoposide) chemotherapy reported complete response(CR) rate and 3-year overall survival(OS) of these patients were 57.1%and 56%respectively. We assumed autologous stem cell transplantation may further improve the prognosis of these patients. Aims: We conducted this clinical trial to address the efficacy and safety of our treatment strategy, GLIDE induction followed by ASCT, in newly diagnosed stage IV and relapsed ENKTL. Methods: We treated 60 patients with newly diagnosed stage IV(n=49) and relapsed(n=11) ENKTL from 2010 to 2016. The median age at recruitment was 38 years and the median follow-up period was 13.4 months. Patients were treated with GLIDE (gemcitabine 800 mg/m2D1,5; L-asparaginase 6000 u/m2D4,6,8,10,12 or peg-asparaginase 2500 u/m2D4,11; ifosfamide 1000 mg/m2D1-3; dexamethasone 20mg D1-4; etoposide 100 mg/m2D1-3) every 4 weeks, and responses were evaluated with PET/CT every 2 cycles. Patients achieving CR underwent ASCT or continued with GLIDE up to 6 cycles. Others finished 6 cycles of GLIDE. Overall response rate(ORR), CR, OS and progression free survival(PFS) were calculated using standard methods. Statistical analysis was done using Fishers exact test or Chi-square test/Kruskal-Wallis test. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Results: Fifty-seven patients had finished planed treatment with 1 withdraw of informed consent after cycle 1, and 2 death of sepsis during cycle 1 and cycle 2 respectively. Twenty-one patients underwent ASCT. The ORR was 81.4%and the CR was 69.5%with early CR (CR after 2 cycles) of 57.6%. Estimated 5-year OS and PFS rates of the whole cohort and patients underwent ASCT were 68.7%, 54.0%, 79.6%and 85.2%respectively. Univariate analysis revealed that ECOG =2 was an independent risk factor for disease progression (HR=4.321, 95%CI 1.127, 16.572, P=0.033) and death (HR=46.254, 2.150, 993.190, P=0.014) and ASCT was associated with better PFS (HR=0.058, 95%CI 0.007, 0.495, P=0.009) and OS (HR=0.019,95%CI 0.001, 0.596, P=0.024). Figure 1 highlights the OS and PFS of whole cohort (A) and ASCT patients (B). Myelosuppression was the most common adverse reaction(AE). The incidences of level 4 neutropenia, thrombocytopenia and anemia were 46.6%, 28.6%and 5.3%respectively. The most common non-hematologic AE was fever with neutropenia (36.5%of total cycles), while others were mild and manageable.(Figure presented) Summary/Conclusions: GLIDE is an effective regiment for newly diagnosed stage IV and relapsed ENKTL. Up-front ASCT after achieving CR can reduce relapse and prolong survival. Treatment related adverse reactions and support care need concerns.