{"entity":{"id":"ddgp-vs-smile-enktl","kind":"trial","name":"DDGP versus SMILE","aka":["CTTNKTL-III/IV","DDGP regimen","Pegaspargase-based versus L-asparaginase-based chemotherapy in advanced NK/T-cell lymphoma"],"tldr":"In advanced NK/T-cell lymphoma, a gentler regimen built on pegylated asparaginase kept the disease controlled for longer than SMILE, the regimen it was compared with, and caused fewer dangerously low white cell counts.","summary":"SMILE showed that an asparaginase-based regimen works in extranodal NK/T-cell lymphoma, where anthracyclines fail, but it is toxic: in its own phase 2 study grade 4 neutropenia occurred in 92 per cent. This open-label randomised trial at 12 hospitals in China, run from January 2011 to February 2019, compared it with DDGP, which keeps the asparaginase (as pegaspargase) and replaces the methotrexate, ifosfamide and etoposide with cisplatin and gemcitabine.\n\nThe final report (Wang and colleagues, JAMA Oncology 2022) randomised 87 patients, of whom 80 were treated, 40 in each arm; median age 43. At a median follow-up of 41.5 months, median progression-free survival was not reached with DDGP against 6.8 months with SMILE (hazard ratio 0.42, 95 per cent confidence interval 0.23 to 0.77, p = 0.004), and median overall survival was not reached against 75.2 months (hazard ratio 0.41, 0.19 to 0.89, p = 0.02). Three-year progression-free survival was 56.6 against 41.8 per cent and five-year overall survival 74.3 against 51.7 per cent. Grade 3 and 4 leukopenia occurred in 62.5 against 85.0 per cent. An interim report of the first 42 patients had appeared in Clinical Cancer Research in 2016.\n\nThe authors call the result promising preliminary evidence and say a confirmation trial in a larger population is warranted. It is the randomised trial behind the statement on the entity page that gentler asparaginase regimens such as DDGP are widely used in China.","status":"positive","asOf":"2026-11-03","links":[{"label":"ClinicalTrials.gov NCT01501149","url":"https://clinicaltrials.gov/study/NCT01501149"},{"label":"JAMA Oncology 2022","url":"https://doi.org/10.1001/jamaoncol.2022.1968"}],"tags":["lymphoma-evidence-entities"],"related":[],"cancers":["extranodal-nk-t-cell-lymphoma","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["dexamethasone","cisplatin","gemcitabine","asparaginase","methotrexate","ifosfamide","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["pfs","orr","hazard-ratio"],"trials":["smile-enktl"],"people":[],"bottlenecks":[],"keyPapers":["paper-ddgp-vs-smile-nk-t-cell-lymphoma-jama-oncol-2022","paper-ddgp-vs-smile-nk-t-cell-lymphoma-clin-cancer-res-2016"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01501149","phase":"4","setting":"Newly diagnosed stage III or IV extranodal NK/T-cell lymphoma, aged 14 to 70: six cycles of DDGP (dexamethasone, cisplatin, gemcitabine, pegaspargase) against six cycles of SMILE","sponsor":"Mingzhi Zhang (First Affiliated Hospital of Zhengzhou University)","result":"Progression-free survival hazard ratio 0.42 and overall survival hazard ratio 0.41 in favour of DDGP over SMILE, with less grade 3 and 4 leukopenia.","started":"2011-01","yearReported":2022,"enrolled":87,"enrolledBasis":"randomised","enrolledNote":"The registry records 80 enrolled, the number treated; the final report randomised 87, of whom 80 received treatment, 40 in each arm.","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"DDGP","n":40,"note":"median not reached; 3-year rate 56.6 per cent"},{"name":"SMILE","n":40,"value":6.8,"note":"median 6.8 months; 3-year rate 41.8 per cent"}],"hr":0.42,"ci":[0.23,0.77],"p":"0.004","source":"https://doi.org/10.1001/jamaoncol.2022.1968"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"DDGP","n":40,"note":"median not reached; 5-year rate 74.3 per cent"},{"name":"SMILE","n":40,"value":75.2,"note":"median 75.2 months; 5-year rate 51.7 per cent"}],"hr":0.41,"ci":[0.19,0.89],"p":"0.02","source":"https://doi.org/10.1001/jamaoncol.2022.1968"},{"endpoint":"Overall response rate","unit":"%","arms":[{"name":"DDGP","n":40,"value":90},{"name":"SMILE","n":40,"value":60}],"p":"0.002","source":"https://doi.org/10.1001/jamaoncol.2022.1968"}],"replication":"Not repeated outside the sponsoring group; the authors themselves ask for a larger confirmatory trial. The registry lists the study as phase 4 and its status as unknown."},"route":"/trials/ddgp-vs-smile-enktl/","neighbours":{"cancer":[{"id":"extranodal-nk-t-cell-lymphoma","kind":"cancer","name":"Extranodal NK/T-cell lymphoma","route":"/cancers/extranodal-nk-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"asparaginase","kind":"drug","name":"Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)","route":"/drugs/asparaginase/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"dexamethasone","kind":"drug","name":"Dexamethasone","route":"/drugs/dexamethasone/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"ifosfamide","kind":"drug","name":"Ifosfamide","route":"/drugs/ifosfamide/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"}],"term":[{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"smile-enktl","kind":"trial","name":"SMILE","route":"/trials/smile-enktl/"}],"paper":[{"id":"paper-ddgp-vs-smile-nk-t-cell-lymphoma-clin-cancer-res-2016","kind":"paper","name":"DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China","route":"/key-papers/paper-ddgp-vs-smile-nk-t-cell-lymphoma-clin-cancer-res-2016/"},{"id":"paper-ddgp-vs-smile-nk-t-cell-lymphoma-jama-oncol-2022","kind":"paper","name":"Efficacy and Safety of a Pegasparaginase-Based Chemotherapy Regimen vs an L-asparaginase-Based Chemotherapy Regimen for Newly Diagnosed Advanced Extranodal Natural Killer/T-Cell Lymphoma: A Randomized Clinical Trial","route":"/key-papers/paper-ddgp-vs-smile-nk-t-cell-lymphoma-jama-oncol-2022/"}]}}