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

Introduction: Long‐term survival of advanced‐stage and relapsed extranodal NK/T cell lymphoma (ENKTL) is 33%‐45%. 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. The role of ASCT as consolidation in these patients is unclear. To address this issue, we analyzed the efficacy and safety of our treatment strategy, GLIDE induction followed by ASCT, in newly diagnosed stage IV and relapsed ENKTL. Patients and 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 followup period was 13.4 months. Patients were treated with GLIDE 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 ≤1, IPI ≤2, early CR and ASCT were associated with less relapse and death. Multivariate analysis showed 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 is 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). (Figure Presented) 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. 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.