Improved prognosis of advanced-stage extranodal NK/T-cell lymphoma: results of the NKEA-Next study

Abstract

A retrospective study of extranodal natural killer/T-cell lymphoma (ENKL) patients diagnosed between 2014 and 2021 in Japan was conducted. Among 351 patients with sufficient data, 116 (33%) were in the advanced stage (5 in stage III and 111 in stage IV) at diagnosis, and were further analyzed. The median age was 60 years (range: 19-90), and 68 (59%) were male. Ninety-four (85%) of stage IV patients had two or more extranodal involvements. The most common first-line regimen was SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide; 52%). The 2-year overall survival (OS) for all patients was 38.5%, which was significantly improved after 2017 (25.2% for 2014-2017 vs. 50.7% for 2018-2021; P = 0.008). Patients treated with SMILE showed better OS than those treated with DeVIC or CHOP (2y-OS: 57.1%, 35.8%, and 0%, respectively; P < 0.001). The prognosis was significantly better in patients who received hematopoietic stem cell transplantation (HSCT) than in those who did not (2-year OS: 68.3% vs. 17.6%, P < 0.001). Multivariate analysis showed SMILE and HSCT were significant factors for OS. In conclusion, the prognosis of advanced-stage ENKL has improved in recent years. The L-asparaginase-containing chemotherapy and subsequent HSCT is considered the recommended strategy.

Fig. 1. Proportions of first-line treatments.

The most common first-line chemotherapy regimen for 106 patients with advanced-stage ENKL was SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide; n = 55, 52%) with or without radiotherapy (RT), followed by DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin; n = 31, 29%), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), including CHOP-like regimen (n = 11, 10%), and other non-anthracycline-containing regimens such as GDP (gemcitabine, dexamethasone, and cisplatin) and GCD (gemcitabine, carboplatin, and dexamethasone).

Fig. 2. Response by the chemotherapeutic regimens.

The overall response rate (ORR) of patients who received SMILE was 71%, and the complete response (CR) rate was 49%. The ORR of DeVIC, CHOP/other regimens, and radiotherapy (RT)/single-agent chemotherapy was 58%, 14%, and 0%, respectively. The CR rate of DeVIC and CHOP/other regimens was 26% and 14%, respectively.

Fig. 3. Survival curves of advanced-stage extranodal NK/T-cell lymphoma.

A The 1-year and 2-year overall survival (OS) of all patients was 53.7% and 38.5%, respectively. The median OS was 13.2 months (95% CI 9.3–22.7). B The 2-year OS was 25.2% for patients diagnosed in 2014–2017 and 50.7% for those diagnosed in 2018–2021. C The 2-year OS was 58.1% for patients treated with SMILE was 58.1%, but was 37.1% for those with DeVIC, and 0% for those with CHOP/other regimens. D The 2-year OS was 68.3% for patients who received HSCT, but was 17.6% for those who did not. E The OS of patients who underwent upfront and salvage HSCT was not significantly different (2-year OS: 73.7% vs. 54.0%). F The 2-year OS was73.1% for patients treated with SMILE followed by HSCT. In contrast, it was 50.0% for patients treated with SMILE without HSCT, 24.0% for those with non-SMILE regimen and HSCT, and 18.5% for those with non-SMILE regimen without HSCT.