Modified SMILE (mSMILE) and intensity-modulated radiotherapy (IMRT) for extranodal NK-T lymphoma nasal type in a single-center population

Abstract

A modification of the SMILE regimen with dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide (mSMILE) followed by Intensity-Modulated Radiotherapy (IMRT) at lower than usual dose, has been adopted as standard of care for extranodal NK-/T-cell lymphoma (ENKL) at our institution. mSMILE is a short course, intensive regimen incorporating pegylated asparaginase. Here, we describe clinical details, outcome and safety of patients receiving mSMILE. Among 28 patients with ENKL treated, response post-mSMILE was 93% (CR 68%), response post IMRT was 95% (CR 87.5%). Among early-stage patients/low PINK-E (n = 13), overall survival (OS) was 100% at the median follow-up of 31 months; progression-free survival (PFS) was 92%. Advanced-stage and intermediate/high PINK-E patients fared similarly (OS 43%, PFS 33.3% at the median follow-up). Thirty-two percent of the patients experienced G3-4 non-hematologic toxicity, all experienced hematologic toxicity. Most localized-stage patients achieved long-term disease control. Despite high response rates, most of the advanced stage patients relapsed quickly.

Keywords:

• Lymphocytes
• NK cell biology
• NK-T cell lymphoma
• mSMILE
• asparaginase

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. SMH reports grants and personal fees from Aileron, Seattle Genetics, Takeda, Kyowa Hakka Kirin, Verastem, Portola, Corvus, Celgene, Spectrum, Forty-Seven, outside of the submitted work. ML received research support from: Celgene, Curis, Jannsen Scientific Affairs, LLC, Juno Therapeutics, MiRagen, TG Therapeutics, ML consulted for AbbVie, Bayer, Celgene, DAVA, Gilead Sciences, Inc, Janssen, Juno Therapeutics, Kite, Novartis, OncLive, Portola, Seattle Genetics, Spectrum, TG Therapeutics. AM reports grants and personal fees from: Seattle Genetics, Bristol-Myers Squibb, Kyowa Hakko Kirin Pharma, Miragen Therapeutics, Takeda Pharmaceuticals, ACD Therapeutics, Cell Medica, Erytech Pharma, Seattle Genetics, Merck and Company, Incyte. AD reports grants and personal fees from Roche, Novartis AG, Seattle Genetics, Celgene, Corvus. BI was supported by the Mortimer J. Lacher lymphoma fellowship.

Disclosure statement

Dr. Dogan reports grants from Seattle Genetics, grants and personal fees from Roche, Corvus Pharmaceuticals, Takeda, EUSA pharma, AbbVie, grants from National Cancer Institute, outside the submitted work. Dr. Horwitz reports grants from ADCT Therapeutics, grants and personal fees from Aileron, Celgene, Forty Seven, Infinity/Verastem, Kyowa Hakka Kirin, Millennium/Takeda, Seattle Genetics, Trillium, Corvus, Innate Pharma, Mundipharma, Portola, Beigene, C4 Therapeutics, Daiichi Sankyo, GlaxoSmithKline, Janssen, Kura Oncology, Miragen, Myeloid Therapeutics, Verastem, Vividion Therapeutics, Affirmed, ASTEX, outside the submitted work. Dr. Lunning reports personal fees from AstraZeneca, grants and personal fees from Bristol Meyers Squibb, Aeratech, Beigene, Curis, Gilead, Janssen, Karyopharm, Kite, Novartis, TG Therapeutics, Verastem, Acrotech, ADC Therapeutics, Legend, outside the submitted work. Dr. Moskowitz reports grants from Seattle Genetics, Incyte, Bristol-Myers Squibb, Merck, Imbrium Therapeutics, Miragen Therapeutics, Seattle Genetics, outside the submitted work. Dr. Straus reports personal fees from Seattle Genetics, Takeda Pharmaceuticals, Karyopharm Therapeutics, outside the submitted work. Drs. Ghione, Qi, Imber, Dahi, Seshan, Sauter, Galasso and Yahalom have nothing to disclose.