A Phase II Study of MESA Chemotherapy for Newly Diagnosed, Relapsed or Refractory Extranodal Natural Killer (NK)/T-Cell Lymphoma, Nasal Type: A Multicenter Trial of Northern-West of China

Purpose/Background: The nasal type of extranodal natural killer NK/T‑cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. There is currently no standard treatment. To explore a more effective and feasible treatment for newly diagnosed, relapsed, or refractory NKTCL, we conducted a phase II study of the steroid (Methotrexate, etoposide, dexamethasone, Polyehylene glycol-asparaginase, MESA) regimen and investigated its efficacy and toxicity.

Patients and Methods:Patients with newly diagnosed, relapsed, or refractory disease were treated in 5 medical centers. The performance status of 0 to 2 were eligible. At least three cycles of MESA chemotherapy + radiotherapy (RT) + three cycles of MESA chemotherapy were administered as the protocol treatment. The primary endpoints were the complete response (CR) rate, partial response (PR), the overall response rate (ORR), and toxicities. Secondary endpoints were overall survival (OS) and progression-free survival (PFS) rate.

Results: A total of 46 eligible patients were enrolled. The median age was 46.1 years (range, 16 to 54 years), and the male: female ratio was 36:10. Among the 35 new diagnosed patients with first-line MESA treatment, the CR/PR at 1 cycle, 2 cycle and 3 cycle was 42.4%/55.9%, 46.9%/50% and 64%/32%, respectively; The ORR was 97.1%, 93.9% and 92.3%. Among 11 relapsed or refractory patients with second-line MESA, the CR/PR at 1 cycle, 2 cycle and 3 cycle was 9.1%/90.9%, 20%/80% and 22.2%/55.6%, respectively; The ORR was 100%, 90.9% and 77.8%. For 35 new diagnosed patients , the 0.5 year, 1 year, 1.5 year, 2 year-OS/PFS was 88.6%/75%, 90%/80%, 92.9%/92.9%, 100%/85.7%, respectively. For 11 relapsed or refractory patients, the 0.5 year, 1 year, 1.5 year, 2 year-OS/PFS was 100%/2.17%, 91.7%/8.7%, 40%/4.3%, 0%/0%, respectively. For 8 advance(IV stage newly diagnosed) NKTCL and 8 relapsed/refractory NKTCL, CR rate was 37.5%(n=6) after 3 cycle MESA, which was less than that of other studies such as SMILE and GELA/GOELAMS. However, PR rate 56.3%(n=9),ORR 93.8%(n=15) and 2y OS rate 81.3%(n=13) were higher than that of other studies. It was showed that different stages had different CR rate and PFS rate. However, the OS had no difference. it was also showed that patients with Ki67≥60% had lower 3 cycle-CR rate and 1 year OS/PFS rate than that of Ki67＜60%. Grade 1 and 2 toxicities were frequent during MESA treatment. 4 patients developed grade1/2hypofibrinogenemia. 6 patients experienced grade 3 leukopenia or thrombocytopenia and 3 patients suffered from severe infection. 13 patients had a grade 1/2 abnormal liver function and 1 patient had grade 3 without delay in chemotherapy. Pegaspargase was well tolerated in all of them. No patient developed grade 4 adverse effects. There were no treatment-related deaths.

Conclusion:

The initial results of MESA chemotherapy for aggressive newly diagnosed, relapsed or refractory NKTCL this type of lymphoma were very encouraging with high effect and safety. These results will require further investigation in larger prospective trials.