Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L-asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T-cell lymphoma: A French retrospective study.


Journal

British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544

Informations de publication

Date de publication:
05 2023
Historique:
revised: 24 01 2023
received: 24 11 2022
accepted: 27 01 2023
medline: 4 5 2023
pubmed: 18 2 2023
entrez: 17 2 2023
Statut: ppublish

Résumé

Extranodal NK/T-cell lymphoma, nasal type is a rare and aggressive form of lymphoma, historically associated with poor prognosis. We report here the results of a retrospective multi-centre study evaluating the efficacy of MGAD (methotrexate, gemcitabine, L-asparaginase and dexamethasone) regimen (two cycles) combined with 'sandwich' radiotherapy in 35 patients with localised newly diagnosed extranodal NK/T-cell lymphoma. Thirty-two patients (91%) reached complete remission. With a long median follow-up of 59.6 months, progression-free and overall survival at 2 and 5 years were 71%, 80% and 53%, 73%, respectively. Around one third of the patients experienced relapse within a median time of 14.5 months. Side-effects were manageable with grades 3-4 cytopenias, mucositis and infection in 50%, 24% and 21% of the cases, respectively. Monitoring of asparaginase activity was performed in 13 patients and showed inactivation of the drug in seven (54%) patients. Our results indicate that a short therapy by sandwich MGAD chemoradiotherapy is a tolerable and effective treatment option in localised newly diagnosed extranodal NK/T-cell lymphoma patients.

Identifiants

pubmed: 36799516
doi: 10.1111/bjh.18689
doi:

Substances chimiques

Gemcitabine 0
Asparaginase EC 3.5.1.1
Methotrexate YL5FZ2Y5U1
Dexamethasone 7S5I7G3JQL

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

673-681

Informations de copyright

© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Références

Wang H, Fu B-B, Gale RP, Liang Y. NK−/T-cell lymphomas. Leukemia. 2021;35(9):2460-8.
Tse E, Zhao W-L, Xiong J, Kwong Y-L. How we treat NK/T-cell lymphomas. J Hematol Oncol. 2022;15(1):74.
Reneau JC, Shindiapina P, Braunstein Z, Youssef Y, Ruiz M, Farid S, et al. Extranodal natural killer/T-cell lymphomas: current approaches and future directions. J Clin Med. 2022;11(10):2699.
Ribrag V, Ell Hajj M, Janot F, Girinsky T, Domenge C, Schwaab G, et al. Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx. Leukemia. 2001;15(7):1123-6.
Li Y-X, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol off J Am Soc Clin Oncol. 2006;24(1):181-9.
Wang B, Li X-Q, Ma X, Hong X, Lu H, Guo Y. Immunohistochemical expression and clinical significance of P-glycoprotein in previously untreated extranodal NK/T-cell lymphoma, nasal type. Am J Hematol. 2008;83(10):795-9.
Yong W, Zheng W, Zhu J, Zhang Y, Wang X, Xie Y, et al. L-asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2009;88(7):647-52.
Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011;117(6):1834-9.
Ji J, Liu T, Xiang B, Liu W, He C, Chen X, et al. A study of gemcitabine, l-asparaginase, ifosfamide, dexamethasone and etoposide chemotherapy for newly diagnosed stage IV, relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type. Leuk Lymphoma. 2014;55(12):2955-7.
Wang J-H, Wang L, Liu C-C, Xia ZJ, Huang HQ, Lin TY, et al. Efficacy of combined gemcitabine, oxaliplatin and pegaspargase (P-gemox regimen) in patients with newly diagnosed advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma. Oncotarget. 2016;7(20):29092-101.
Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan clinical oncology group study JCOG0211. J Clin Oncol off J Am Soc Clin Oncol. 2009;27(33):5594-600.
Bi X, Xia Y, Zhang W, Sun P, Liu PP, Wang Y, et al. Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma. Ann Hematol. 2015;94(9):1525-33.
Zang J, Li C, Luo S-Q, Wang JH, Xu M, Zhao LN, et al. Early radiotherapy has an essential role for improving survival in patients with stage I-II nasal-type of NK/T cell lymphoma treated with L-asparaginase-containing chemotherapy-a single institution experience. Ann Hematol. 2015;94(4):583-91.
Tsai H-J, Lin S-F, Chen C-C, Chen TY, Su WC, Hwang WL, et al. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015;94(2):130-7.
Michot J-M, Mazeron R, Danu A, Lazarovici J, Ghez D, Antosikova A, et al. Concurrent etoposide, steroid, high-dose Ara-C and platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma, nasal type. Eur J Cancer. 2015;51(16):2386-95.
Li J, Li Y, Zhong M, Liu W, Liu X, Li J, et al. A multicenter retrospective comparison of sequential versus Sandwich Chemoradiotherapy for stage IE-IIE Extranodal natural killer/T-cell lymphoma, nasal type. J Cancer. 2018;9(9):1598-606.
Kwong YL, Kim SJ, Tse E, Oh SY, Kwak JY, Eom HS, et al. Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma. Ann Oncol off J Eur Soc Med Oncol. 2018;29(1):256-63.
Wang H-Y, Niu S-Q, Yang Y-Y, Li YY, Chen HB, Zhang YJ. Promising clinical outcomes of sequential and “Sandwich” chemotherapy and extended involved-field intensity-modulated radiotherapy in patients with stage IE /IIE extranodal natural killer/T-cell lymphoma. Cancer Med. 2018;7(12):5863-9.
Ahn HK, Kim SJ, Hwang DW, Ko YH, Tang T, Lim ST, et al. Gemcitabine alone and/or containing chemotherapy is efficient in refractory or relapsed NK/T-cell lymphoma. Invest New Drugs. 2013;31(2):469-72.
Zhou Z, Li X, Chen C, Li X, Zhang L, Li L, et al. Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients. Ann Hematol. 2014;93(11):1889-94.
Wei W, Wu P, Li L, Zhang Z-H. Effectiveness of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) chemotherapy combined with radiotherapy in newly diagnosed, stage IE to IIE, nasal-type, extranodal natural killer/T-cell lymphoma. Hematol Amst Neth. 2017;22(6):320-9.
Liu T, Zhu F, Xiao Y, Li Q, Liu X, Yang K, et al. Pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy is effective for newly diagnosed extranodal NK/T-cell lymphoma: a retrospective study. Cancer Manag Res. 2018;10:5061-9.
Laurent C, Baron M, Amara N, Haioun C, Dandoit M, Maynadié M, et al. Impact of expert pathologic review of lymphoma diagnosis: study of patients from the French Lymphopath network. J Clin Oncol off J Am Soc Clin Oncol. 2017;35(18):2008-17.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987-94.
Kim SJ, Yoon DH, Jaccard A, Chng WJ, Lim ST, Hong H, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol. 2016;17(3):389-400.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol off J Am Soc Clin Oncol. 2014;32(27):3059-68.
Yoon DH, Kim SJ, Jeong SH, Shin DY, Bae SH, Hong J, et al. Phase II trial of concurrent chemoradiotherapy with L-asparaginase and MIDLE chemotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type (CISL-1008). Oncotarget. 2016;7(51):85584-91.
Jiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, et al. Phase 2 trial of “sandwich” L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012;118(13):3294-301.
Xu P-P, Xiong J, Cheng S, Zhao X, Wang CF, Cai G, et al. A phase II study of methotrexate, etoposide, dexamethasone and Pegaspargase sandwiched with radiotherapy in the treatment of newly diagnosed, stage IE to IIE Extranodal natural-killer/T-cell lymphoma, nasal-type. EBioMedicine. 2017;25:41-9.
Jiang M, Zhang L, Xie L, Zhang H, Jiang Y, Liu WP, et al. A phase II prospective study of the “Sandwich” protocol, L-asparaginase, cisplatin, dexamethasone and etoposide chemotherapy combined with concurrent radiation and cisplatin, in newly diagnosed, I/II stage, nasal type, extranodal natural killer/T-cell lymphoma. Oncotarget. 2017;8(30):50155-63.
Zhang L, Jiang M, Xie L, Zhang H, Jiang Y, Yang QP, et al. Five-year analysis from phase 2 trial of “sandwich” chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer Med. 2016;5(1):33-40.
Kim SJ, Yang D-H, Kim JS, Kwak JY, Eom HS, Hong DS, et al. Concurrent chemoradiotherapy followed by L-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study. Ann Hematol. 2014;93(11):1895-901.
Wang L, Wang Z-H, Chen X-Q, Wang K-F, Huang H-Q, Xia Z-J. First-line combination of GELOX followed by radiation therapy for patients with stage IE/IIE ENKTL: an updated analysis with long-term follow-up. Oncol Lett. 2015;10(2):1036-40.
Lee J, Suh C, Park YH, Ko YH, Bang SM, Lee JH, et al. Extranodal natural killer T-cell lymphoma, nasal-type: a prognostic model from a retrospective multicenter study. J Clin Oncol off J Am Soc Clin Oncol. 2006;24(4):612-8.
Wang L, Wang H, Wang J, Xia ZJ, Lu Y, Huang HQ, et al. Post-treatment plasma EBV-DNA positivity predicts early relapse and poor prognosis for patients with extranodal NK/T cell lymphoma in the era of asparaginase. Oncotarget. 2015;6(30):30317-26.
Liu Z-L, Bi X-W, Liu P-P, Lei D-X, Jiang W-Q, Xia Y. The clinical utility of circulating Epstein-Barr virus DNA concentrations in NK/T-cell lymphoma: a meta-analysis. Dis Markers. 2018;2018:1961058.
Wang X-X, Li P-F, Bai B, Gao Y, Rong QX, Cai QQ, et al. Differential clinical significance of pre-, interim-, and post-treatment plasma Epstein-Barr virus DNA load in NK/T-cell lymphoma treated with P-GEMOX protocol. Leuk Lymphoma. 2019;60(8):1917-25.
Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, et al. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood. 2010;115(7):1351-3.
Salzer W, Bostrom B, Messinger Y, Perissinotti AJ, Marini B. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59(8):1797-806.
Huynh VT, Love A, English M, Lin CH. Drug monitoring of Asparaginase activity to detect silent inactivation in pediatric acute lymphoblastic leukemia patients receiving peg-Asparaginase. Blood. 2018;132(Supplement 1):3968.
Jaccard A, Chaubard S, Benoist J-F, Couronne L, Philippe L, Gyan E, et al. Monitoring Asparaginase activity in 21 patients with Extranodal NK/T-cell lymphoma shows a very high proportion of Asparaginase inactivation. Blood. 2018;132(Supplement 1):5351.
Kim HJ, Ock C-Y, Kim TM, Lee SH, Lee JY, Jung S, et al. Comparison of native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in combination with Ifosfamide, methotrexate, etoposide, and prednisolone, in Extranodal NK/T-cell lymphoma, nasal type. Cancer Res Treat. 2018;50(3):670-80.
Sakata K, Fuwa N, Kodaira T, Aratani K, Ikeda H, Takagi M, et al. Analyses of dose-response in radiotherapy for patients with mature T/NK-cell lymphomas according to the WHO classification. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2006;79(2):179-84.
Sun P, Wang Y, Yang H, Chen C, Nie M, Sun XQ, et al. Combination of anti-PD-1 antibody, Anlotinib and Pegaspargase “Sandwich” with radiotherapy in localized natural killer/T cell lymphoma. Front Immunol. 2022;13:766200.

Auteurs

Sammara Chaubard (S)

Hematology Department, Limoges University Hospital, Limoges, France.

Amira Marouf (A)

Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France.

David Lavergne (D)

Hematology Department, Limoges University Hospital, Limoges, France.

François Lemonnier (F)

Hematology Department, Henri Mondor University Hospital, Assistance Publique des Hôpitaux de Paris, INSERM U955, Mondor Institute for Biomedical Research, Paris-Est Créteil University, Créteil, France.

Julien Rossignol (J)

Hematology Department, Necker Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.

Aline Clavert (A)

Hematology Department, Angers University Hospital, Angers, France.

Rémy Gressin (R)

Hematology Department, Grenoble University Hospital, Grenoble, France.

Guillaume Cartron (G)

Hematology Department, University Hospital Center UMR-CNRS 5235, Montpellier, France.

Agathe Waultier-Rascalou (A)

Hematology Department, Nîmes University Hospital, Nîmes, France.

Jacques Vargaftig (J)

Hematology Department, René Huguenin Hospital-Curie Institute, Saint-Cloud, France.

Gilles Salles (G)

Hematology Department, Lyon-Sud Hospital, University of Lyon, Lyon, France.

Emmanuel Bachy (E)

Hematology Department, Lyon-Sud Hospital, University of Lyon, Lyon, France.

Hervé Ghesquières (H)

Hematology Department, Lyon-Sud Hospital, University of Lyon, Lyon, France.

Olivier Tournilhac (O)

Hematology Department, Clermont University Hospital of Clermont-Ferrand, Clermont Auvergne University, Clermont-Ferrand, France.

Adrien Chauchet (A)

Hematology Department, Jean Minjoz University Hospital, Besançon, France.

Steven Le Gouill (S)

Service d'Hématologie Clinique, Hôtel-Dieu, CHU Nantes, INSERM, CNRS, CRCINA Nantes, Université de Nantes, Faculté de Médecine, Nantes, France.

Gandhi Damaj (G)

Hematology Institute, Caen University Hospital, Normandy University, Caen, France.

Luc-Matthieu Fornecker (LM)

Hematology Department, Strasbourg University Hospital, Strasbourg, France.

David Sibon (D)

Hematology Department, Necker Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.

Lucie Obéric (L)

Hematology Department, Toulouse-Oncopole University Cancer Institute (IUCT-O), Toulouse, France.

Jean-Marie Michot (JM)

Gustave Roussy Institute, Département des Innovations Thérapeutiques et Essais Précoces, Université Paris-Saclay, Villejuif, France.

Philippe Gaulard (P)

Pathology Department, Henri Mondor University Hospital, Assistance Publique des Hôpitaux de Paris, INSERM U955, Mondor Institute for Biomedical Research, Paris-Est Créteil University, Créteil, France.

Olivier Hermine (O)

Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France.
Hematology Department, Necker Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.

Lucile Couronné (L)

Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France.
Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.

Arnaud Jaccard (A)

Hematology Department, Limoges University Hospital, Limoges, France.

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