Pilot Study of Peginterferon Alfa-2a (PEGASYS®) Concurrent Administration during Induction Chemoradiotherapy and Maintenance Therapy in Patients with EBV-Associated Extranodal NK/T Cell Lymphoma

Extranodal NK/T-cell lymphoma, nasal type is common in Asians rather than in Western populations. This special subtype responds poorly to intensive chemotherapy regimens or has a significant relapse rate in spite of low IPI and loco-regional staging. The presence of the EBV genome within tumor cells raised the possibility of developing therapeutic strategies directed at viral targets. The primary objectives of this prospective, single center, nonrandomized phase II trial are the evaluation of efficacy by determination of progression-free survival after concurrent administration of peginterferon alfa-2a (PEGASYS®, provided by Roche Korea) and chemoradiotherapy in patients with extranodal NK/T cell lymphoma. In addition, we evaluated the efficacy of peginterferon alfa-2a maintenance therapy for 3 years. All seven patients with newly diagnosed CD56+ EBV+ extranodal NK/T-cell lymphoma were enrolled onto a prospective clinical trial. Step 1; PEGASYS® 180 mcg was administered once weekly on D1, D8 of ProMACE-CytaBOM. 1, 2 cycles. Step 2; PEGASYS® 180 mcg will be administered once weekly on D1, D8, D15, D22 of involved-filed irradiation 3600 cGy (180 cGy × 20, for 4 weeks). Step 3; PEGASYS® 180 mcg will be administered once weekly on D1, D8 of ProMACE-CytaBOM. 3, 4 cycles. Step 4; PEGASYS® 180 mcg will be administered every two weeks after hematologic recovery of high-dose therapy and autologous PBSCT for 3 years. In case of advanced stage and non-nasal lesion, Step 2 was omitted and ProMACE-CytaBOM was extended to 6 cycles. EBV DNA copy based on real-time PCR was monitored. Of all 7 patients, 6 patients achieved complete response and 1 patient was dead due to pneumonia during chemotherapy. With a median follow-up of 26 months (3–36 months), the 3-year PFS were 67%. Of 6 assessable patients, five patients extended to peginterferon alfa-2a maintenance therapy and four patients showed PFS. Among two relapsed patients, one patient refused a peginterferon alfa-2a maintenance therapy and eventually relapsed 3 months later. Titer of EBV DNA copy in whole blood was significantly decreased compared with the titer on initial diagnosis. The main toxicities of peginterferon alfa-2a were mild flu-like symptoms. This pilot study suggests that larger prospective randomized studies are needed to define the role of peginterferon alfa-2a concurrent administration during induction therapy and maintenance therapy in EBV-associated extranodal NK/T-cell lymphoma.