GAD‐M REGIMEN FOR NEWLY DIAGNOSED EXTRANODAL NK/T CELL LYMPHOMA: ANALYSIS OF EFFICACY AND SAFETY FROM PHASE II STUDY (NCT 01991158)

Abstract

Introduction: PEG‐asparaginase‐based chemotherapy regimens have improved the efficacy of extranodal natural killer/T‐cell lymphoma (ENKTL). However, the methotrexate was another important drug for ENKTL, which was contained in both SMILE and AspaMetDex regimens. GELOX regimen lost this drug. Therefore, we evaluated the efficacy and safety for methotrexate with gemcitabine, PEG‐asparaginase and dexamethasone (GAD‐M) regimen in patients with treatment naive ENKTL in the Phase II Study (NCT 01991158). Methods: Patients who were newly diagnosed as ENKTL in stageI‐IV from 18 to 80 years with ECOG PS of 0 ~ 3 were eligible for enrollment. GAD‐M regimen (gemcitabine 1000 mg/m2; ivdrip, d1, d8, PEG‐aspargase 2500 U/m2; im. d1, dexamethasone 20 mg, ivdrip. d1‐3, Methotrexate 3000 mg/ m2; civ 12‐hour, d1) was planned as the protocol treatment. The regimen was repeated every three weeks. For stage I/II patients, 2‐4 cycles of GAD‐M regimen followed by EIFRT and additional 4‐2 cycles. For stage III/IV, GAD‐M regimens were repeated for six cycles. The primary endpoint was overall response rate (ORR) after six cycles of GAD‐M. Secondary endpoints were 3‐year progression‐free survival(PFS), 3‐year overall survival(OS), and toxicity. Response was assessed using the revised International Workshop Criteria. Toxicity was graded according to the CommonTerminology Criteria for Adverse Events v4.0. Results: 41 patients were enrolled from Oct 2013 to Aug 2015. 36 patients were evaluable for response. The baseline clinical characteristics were as follows: the median age, 45 years (range: 18‐75 years); >60 years, 13.5%; female, 30.6%; ECOG PS >1, 13.9%; stageI/II, 86.1%; elevated LDH, 27.8%. After 2 cycles of GAD‐M, ORR in all and stageI/II were 94.4% (34/36) and 100% (31/31), respectively. CR rate were 50% (18/36) and 54.8% (17/31), respectively. After 6 cycles ORR in all and stageI/II were still 94.4% (34/36) and 100%(31/36), respectively. CR rate increased to 83.3% (30/36) and 90.32% (28/ 31), respectively. At median follow‐up of 23.3 months, 3‐year PFS was 72.1%(Figure 1A), 3‐year OS was 76.3% (Figure 1B). According to the stage, 3‐year PFS for stage I/II and III/IV were 77.3% and 40.0%, respectively. 3‐year OS were 79.3% and 60.0%, respectively. The most common hematologic adverse event of grade 3/4 was anemia (52.8%). The major non hematologic side effects were hypoalbuminemia (100%), increased transaminases (88.9%) and hyperbilirubinaemia (52.8%). Although grade 1/2 nonhematologic toxicities were frequent during GAD‐M treatment. Grade 3/4 toxicities (Figure Presented) were few. One patients died of treatment related toxicity, who was 61‐year‐old man died of electrolyte disorders caused by severe vomiting. Other patients didn't suffer from this adverse event. Conclusions: These results demonstrate that GAD‐M regimen provides a high ORR in newly diagnosed ENKTL, especially for stageI/II. GAD‐M with EIFRT for ENKTL in stageI/II was feasible, although most patients experienced recoverable liver dysfunction and anemia during the protocol treatment.