DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients

Wang, Xin; Hu, Jingtian; Meng, Di; Ding, Mengjie; Zhu, Linan; Wu, Jingjing; Sun, Zhenchang; Li, Xin; Zhang, Lei; Li, Ling; Wang, Xinhua; Fu, Xiaorui; Wang, Guannan; Chen, Qingjiang; Zhang, Mingzhi; Zhang, Xudong

doi:10.1111/cts.12893

Cited by 9 publications

(6 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1-year PFS was also higher for DDGP (86%) than for SMILE (38%), p = 0.006. The DDGP regimen showed better tolerability, less leukopenia ( p = 0.030) and less allergic reactions ( p = 0.015) 21 . In opposition, SMILE was associated with higher rate of grade 3/4 adverse events, including diarrhea, mucositis, heart failure, arrhythmias and deaths related to treatment 21 .…”

Section: Discussionmentioning

confidence: 97%

“…The tumor cells of the ENKTL present high P-glycoprotein (Pgp) concentration, which confers a multidrug resistant (MDR) phenotype and resistance to anthracycline-based regimens, the most used treatment in clinical practice for mature T-cell lymphomas 4 , 15 , 16 . Chemotherapy agents attempting to overcome MDR mechanisms such as platinum analogues, ifosfamide, etoposide and asparaginase have demonstrated better responses and improved outcomes when compared to anthracyclines 17 – 21 . Since ENKTL is highly sensitive to radiation, high-dose extended-field radiotherapy (EF-RT) with 50–60 Gy has become a backbone for treatment of early-stage disease 17 , 22 , 23 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project

Lage

Machado

Reichert

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Extranodal natural-killer/T-cell lymphoma (ENKTL) is a rare and aggressive Epstein-Barr virus related mature T-cell and natural-killer malignancy. Although highly prevalent in South America, few studies covering data from this geographic location have been published. Therefore, this study aims to report clinical characteristics, prognostic factors, and outcomes in a multicenter cohort of ENKTL patients from Brazil. This retrospective, observational and multicenter study included 98 ENKTL patients treated during two decades in Brazil. Data were extracted from the T-Cell Brazil Project database. In our cohort, 59/98 patients (60.2%) were male, with a median age of 50 years. Sixty-two patients (63.3%) had B-symptoms, 26/98 (26.5%) had Eastern Cooperative Oncology Group scale ≥ 2; 16/98 (16.3%) presented extranasal disease and 34.7% (34/98) were advanced-stage (Ann Arbor/Cotswolds III/IV). The median follow-up for the whole cohort was 49 months, with an estimated 2-year overall survival (OS) and progression-free survival (PFS) of 51.1% and 17.7%, respectively. In early-stage disease (IE/IIE), the median OS was 21.8 months for patients treated with concurrent radiotherapy plus chemotherapy (CCRT-VIPD [etoposide/vp-16, ifosfamide, cisplatin and dexamethasone), 16.2 months for sequential chemoradiotherapy (SCRT) followed by asparaginase-based regimens, and 56.7 months for SCRT followed by CHOP-like (cyclophosphamide, doxorrubicin, vincristine and prednisone) treatments, p = 0.211. CCRT was associated with higher rates of early-mortality, hematological toxicity, and mucositis. Median OS was 8.2 months for patients with advanced-stage disease receiving regimens containing asparaginase compared to 3.2 months for anthracycline-based therapy, p = 0.851. Chemo-radiotherapy (CRT) regimens demonstrated better OS (p = 0.001) and PFS (p = 0.007) than chemotherapy alone. Multivariate analysis revealed anemia, relapsed/refractory (R/R) disease and radiotherapy omission as poor outcome predictors for OS. Lymphopenia and radiotherapy omission adversely affected PFS. Concerning progression of disease within 24-months (POD-24), clinical stage III/IV was a poor outcome predictor. In this real-life Brazilian cohort, ENKTL presented dismal outcomes. Radiation therapy was an independent factor for increased OS and PFS, but CCRT regimens were associated with higher toxicities. Polychemotherapy based on anti-multi drug resistant agents was not associated with survival benefit in either early or advanced-stage disease in our patient cohort.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project

Lage

Machado

Reichert

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The regimen DDGP (dexamethasone, gemcitabine, cisplatin, and pegylated asparaginase) had been compared prospectively and retrospectively with SMILE. Results purportedly showed that DDGP led to better CR and survivals [ 76 , 77 ]. However, these studies were seriously flawed, because the outcomes of the SMILE cohorts were exceptionally poor, which accounted for the apparent but probably erroneous superiority of the DDGP regimen.…”

Section: Management Of Stage Iii/iv Nasal Nk/t-cell Lymphomasmentioning

confidence: 99%

How we treat NK/T-cell lymphomas

et al. 2022

View full text Add to dashboard Cite

Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein–Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment.

show abstract

“…However, severe adverse events remain an obstacle in clinical practice. Earlier investigations have indicated that approximately 70% of patients with ENKTL experience severe leukopenia (grades 3–4), leading to poor tolerance to treatment [ 29 , 30 ]. Therefore, low-toxicity chemotherapy with radiotherapy, such as RT and a two-thirds dose of DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) chemotherapy (RT-2/3DeVIC), CCRT-VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase), and RT-P-GEMOX, is applied to the treatment of adult ENKTL [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“Sandwich” protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study

Shen

Wan

et al. 2023

Ann Hematol

View full text Add to dashboard Cite

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the “sandwich” regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18–57 months) and 20 months (range: 5–47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.

show abstract

DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients

Cited by 9 publications

References 27 publications

High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project

High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project

How we treat NK/T-cell lymphomas

“Sandwich” protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study

Contact Info

Product

Resources

About