SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group.
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.
Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China. ylkwong@hkucc.hku.hk
Yok-Lam
YL
Kwong
Won Seog
WS
Kim
Soon Thye
ST
Lim
Seok Jin
SJ
Kim
Tiffany
T
Tang
Eric
E
Tse
Anskar Y H
AY
Leung
Chor-Sang
CS
Chim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D054391:Lymphoma, Extranodal NK-T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
D005047:Etoposide; D003907:Dexamethasone; D001215:Asparaginase; D007069:Ifosfamide; D008727:Methotrexate