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Updated: May 19, 2026
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group
Yok-Lam Kwong1, Won Seog Kim, Soon Thye Lim
1Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China. ylkwong@hkucc.hku.hk
Abstract:
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.
Insights
The SMILE regimen shows an 81% response rate for natural killer/T-cell lymphoma, offering a viable treatment option. However, significant toxicities like neutropenia and thrombocytopenia require careful management.
Area of Science:
- Oncology
- Hematology
- Clinical Trials
Background:
- Natural killer/T-cell lymphoma (NKTL) is a rare and aggressive hematologic malignancy with a generally poor prognosis.
- Optimal treatment strategies for NKTL are not well-defined, necessitating further research into effective therapeutic regimens.
Purpose of the Study:
- To evaluate the general applicability and efficacy of the dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) regimen in a broader patient population with newly diagnosed or relapsed/refractory NKTL.
- To assess the response rates, survival outcomes, and toxicity profile of the SMILE regimen in a diverse group of NKTL patients.
Main Methods:
- A cohort of 43 newly diagnosed and 44 relapsed/refractory NKTL patients received the SMILE regimen.
- Patient characteristics, including disease stage, prognostic scores, and demographic factors, were recorded.
- Treatment response, overall survival, disease-free survival, and adverse events were monitored and analyzed.
Main Results:
- The overall response rate (ORR) to the SMILE regimen was 81% upon treatment completion (66% complete remission, 15% partial remission).
- Significant toxicities included grade 3/4 neutropenia (57 patients, 5 sepsis-related deaths), grade 3/4 thrombocytopenia (36 patients), and nephrotoxicity (15 patients).
- The 5-year overall survival was 50%, and the 4-year disease-free survival was 64%, with the International Prognostic Index identified as a significant prognostic factor.
Conclusions:
- The SMILE regimen demonstrates a high overall response rate in both newly diagnosed and relapsed/refractory NKTL patients, suggesting its broad applicability.
- While effective, the SMILE regimen is associated with significant toxicities, including neutropenia and thrombocytopenia, necessitating vigilant monitoring and management.
- The International Prognostic Index remains a critical factor influencing outcomes in NKTL patients treated with the SMILE regimen.
