SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group

• Published in: Blood Vol. 120; no. 15; pp. 2973 - 2980
• Main Authors: Kwong, Yok-Lam, Kim, Won Seog, Lim, Soon Thye, Kim, Seok Jin, Tang, Tiffany, Tse, Eric, Leung, Anskar Y.H., Chim, Chor-Sang
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 11.10.2012; Americain Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - administration & dosage; Biological and medical sciences; Clinical Trials, Phase II as Topic; Cohort Studies; Dexamethasone - administration & dosage; Drug Resistance, Neoplasm - drug effects; Etoposide - administration & dosage; Female; Hematologic and hematopoietic diseases; Humans; Ifosfamide - administration & dosage; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Extranodal NK-T-Cell - drug therapy; Lymphoma, Extranodal NK-T-Cell - mortality; Lymphoma, Extranodal NK-T-Cell - pathology; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Prognosis; Survival Rate; Young Adult; Asia; Natural killer T cell; Hematology; Lymphoproliferative syndrome; Treatment efficiency; Malignant hemopathy; Lymphoid neoplasm; Lymphoma; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-05-431460

Natural killer/T-cell lymphoma is rare and aggressive, with poor outcome. Optimal treatment remains unclear. A novel regimen dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) showed promise in phase 1/2 studies with restrictive recruitment criteria. To define the general applicability of SMILE, 43 newly diagnosed and 44 relapsed/refractory patients (nasal, N = 60, nonnasal, N = 21; disseminated, N = 6; male, N = 59; female, N = 28) at a median age of 51 years (23-83 years) were treated. Poor-risk factors included stage III/IV disease (56%), international prognostic index of 3 to 5 (43%), and Korean prognostic scores of 3 to 4 (41%). A median of 3 (0-6; total = 315) courses of SMILE were administered. Significant toxicities included grade 3/4 neutropenia (N = 57; 5 sepsis-related deaths); grade 3/4 thrombocytopenia (N = 36); and nephrotoxicity (N = 15; 1 acute renal failure and death). Interim analysis after 2 to 3 cycles showed complete remission rate of 56%, partial remission rate of 22%, giving an overall response rate of 78%. On treatment completion, the overall-response rate became 81% (complete remission = 66%, partial remission = 15%). Response rates were similar for newly diagnosed or relapsed/refractory patients. At a median follow-up of 31 months (1-84 months), the 5-year overall survival was 50% and 4-year disease-free-survival was 64%. Multivariate analysis showed that international prognostic index was the most significant factor impacting on outcome and survivals.