The outcome of modified‐smile regimen as the first‐line treatment for newly diagnosed frail advanced high‐risk nk/t cell lymphoma: a retrospective observation study

Introduction: To explore an effective and well-tolerant treatment for newly diagnosed advanced high-risk extranodal natural killer/T cell lymphoma (NKTCL) patients with poor performance status. We analyzed the efficacy and toxicity of modified-SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) regimen in untreated advanced high-risk NKTCL patients retrospectively. Methods: Ten newly diagnosed advanced high-risk extranodal natural killer/T cell lymphoma (NKTCL) patients with a performance status of 2 were included in Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2017 to May 2019. At least two cycles of modified-SMILE chemotherapy were administered as the first-line treatment. The primary endpoint was overall survival (OS) and progression-free survival (PFS). The secondary endpoint was the adverse effects of the treatment. Results: A total of 10 patients with newly diagnosed advanced high-risk NKTCL were enrolled, with a median age of 31.5 years (18-57 years). The male: female ratio was 7:3. The performance status of all patients was 2. Seven patients had B symptoms at the initial diagnosis, all presenting as hyperpyrexia. Extranodal organs involvement at the initial diagnosis included nasal cavity (8/10), skin (5/10), bone (4/10), lung (3/10), breast (2/10), pancreas (2/10), liver (1/10), stomach (1/10), intestine (2/10), adrenal glands (1/10) and uterine adnexa (1/10). Bone marrow involvement was present in 3 patients, and the spleen was involved in 2 patients. The prognostic index of NKTCL with Epstein-Barr virus DNA (PINK-E) of all patients was higher than 3. The median OS and PFS were 9 months (2-53 months) and 3 months (1-53 months), respectively. The main adverse effects were hematological toxicities including neutropenia, thrombocytopenia, and decreased fibrinogen. The grade 3/4 neutropenia happened in 2 patients, and the grade 4 thrombocytopenia happened in 1 patient. All toxicities were tolerable. To Mar 2023, the median follow-up period was 9 months (2-53 months), and the median OS was 9 months (2-53 months). Nine patients died and 1 patient survived. Of the 9 patients who died, all patients were diagnosed with Lymphoma-associated haemophilic syndrome (LAHS). Conclusions: The prognosis of advanced high risk NKTCL is very poor because of the poor tolerance to the intensive chemotherapy and the high incidence of LAHS. The modified-SMILE regimen might be an effective and well-tolerance chemotherapy to this intractable condition. Keywords: Chemotherapy, Combination Therapies No conflicts of interests pertinent to the abstract.