medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-19-101-105medsovet-2755Research ArticleОНКОГЕМАТОЛОГИЯONCOHEMATOLOGYБрентуксимаб ведотин – первый таргетный препарат в лечении лимфомы ХоджкинаBrentuximab vedotin is the first target drug in the treatment of hodgkin lymphomaТумянГ. С.TumyanG. S.

д.м.н., профессор кафедры онкологии РМАНПО Минздрава России, ведущий научный сотрудник отделения химиотерапии гемобластозов ФГБУ НМИЦ онкологии им. Н.Н. Блохина МЗ РФ

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, МоскваРоссияBlokhin Russian Cancer Research Center of the Ministry of Health of Russia, MoscowRussian Federation201811112018019101105Copyright © Тумян Г.С., 20182018Тумян Г.С.Tumyan G.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2755

Успехи в лечении лимфомы Ходжкина относятся к наиболее значимым достижениям онкологии нашего времени. Тем не  менее примерно в 15–20% случаев имеет место ранний рецидив или рефрактерное течение заболевания. Именно у этой категории больных впервые успешно был применен таргетный препарат брентуксимаб ведотин. Это гуманизированное моноклональное антитело, специфичное к антигену CD30 на поверхности опухолевых клеток, к которому посредством чувствительного к протеазам линкера присоединен цитостатический агент монометилауристатин Е, мощный ингибитор тубулина. В данной статье представлена характеристика антигена CD30 и нового препарата, а также клинические данные, подтверждающие его эффективность, результаты крупных обзоров и научных исследований по использованию брентуксимаба ведотина в монорежиме и в комбинации на разных этапах лечения лимфомы Ходжкина.

 

Progress in the treatment of Hodgkin lymphoma are among the most significant achievements of oncology of our age. Nevertheless, an early relapse or refractory course of the disease account for approximately 15–20% of cases. It was this category of patients, in which the target drug brentuximab vedotin was successfully used for the first time. This is an anti-CD30 (a cell surface antigen) humanized monoclonal antibody conjugated via a protease-cleavable linker to the cytostatic agent monomethyl auristatin E, the potent tubulin inhibitor. This article describes the characteristics of CD30 antigen and a new preparation, as well as clinical data confirming its efficacy, the results of major reviews and research on the use of brentuximab vedotin in mono and combination therapy regimens at the different stages of treatment for Hodgkin lymphoma.

лимфома Ходжкинаантиген CD30брентуксимаб ведотинHodgkin lymphomaCD30 antigenbrentuximab vedotinReferencesvan der Weyden CA, Pileri S, Feldman A, Whisstock J, Prince H. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. Blood Cancer J, 2017 Sep, 7(9): e603.van der Weyden CA, Pileri S, Feldman A, Whisstock J, Prince H. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. Blood Cancer J, 2017 Sep, 7(9): e603.Schneider C, Hubinger G. Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family. Leuk Lymphoma, 2002, 43: 1355–1366.Schneider C, Hubinger G. Pleiotropic signal transduction mediated by human CD30: a member of the tumor necrosis factor receptor (TNFR) family. Leuk Lymphoma, 2002, 43: 1355–1366.Duckett CS, Gedrich RW, Gilfillan MC, Thompson CB. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol, 1997, 17: 1535–1542.Duckett CS, Gedrich RW, Gilfillan MC, Thompson CB. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol, 1997, 17: 1535–1542.Zheng B, Fiumara P, Li YV, Georgakis G, Snell V, Younes M et al. MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival. Blood, 2003, 102: 1019–1027.Zheng B, Fiumara P, Li YV, Georgakis G, Snell V, Younes M et al. MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival. Blood, 2003, 102: 1019–1027.Maeda N, Muta H, Oflazoglu E, Yoshikai Y. Susceptibility of human T-cell leukemia virus type I-infected cells to humanized anti-CD30 monoclonal antibodies in vitro and in vivo. Cancer Sci, 2010, 101: 224–230.Maeda N, Muta H, Oflazoglu E, Yoshikai Y. Susceptibility of human T-cell leukemia virus type I-infected cells to humanized anti-CD30 monoclonal antibodies in vitro and in vivo. Cancer Sci, 2010, 101: 224–230.Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res, 2002, 62: 3736–3742.Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res, 2002, 62: 3736–3742.Forero-Torres A, Leonard JP, Younes A, Rosenblatt JD, Brice P, Bartlett NL et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol, 2009, 146: 171–179.Forero-Torres A, Leonard JP, Younes A, Rosenblatt JD, Brice P, Bartlett NL et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol, 2009, 146: 171–179.Iordanis Gravanis. The European Medicines Agency review of Brentuximab Vedotin (Adcetris) for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma or systemic anaplastic large cell lymphoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Oncologist, 2016 Jan, 21(1): 102–109.Iordanis Gravanis. The European Medicines Agency review of Brentuximab Vedotin (Adcetris) for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma or systemic anaplastic large cell lymphoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use. Oncologist, 2016 Jan, 21(1): 102–109.Younes A, Barlett N, Leonard J et al. Brentuximab Vedotin (SGN-35) for relapsed CD30+ lymphomas. N Engl J Med, 2010, 363: 1812-1821.Younes A, Barlett N, Leonard J et al. Brentuximab Vedotin (SGN-35) for relapsed CD30+ lymphomas. N Engl J Med, 2010, 363: 1812-1821.Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol, 2012, 30: 2183–2189.Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol, 2012, 30: 2183–2189.Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2015, 385: 1853–1862.Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2015, 385: 1853–1862.Younes A, Connors JM, Park S, Fanale M, O’Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol, 2013 Dec, 14(13): 1348-56.Younes A, Connors JM, Park S, Fanale M, O’Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol, 2013 Dec, 14(13): 1348-56.Connors JM, Jurczak W, Straus DJ et al. Brentuximab Vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med, 2018 Jan 25, 378(4): 331–344.Connors JM, Jurczak W, Straus DJ et al. Brentuximab Vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med, 2018 Jan 25, 378(4): 331–344.Garcia-Sanz R, Sureda A, Gonzalez A, De la Cruz F, Sanchez-Gonzalez B et al. Brentuximab Vedotin plus ESHAP (BRESHAP) is a highly effective combination for inducing remission in refractory and relapsed Hodgkin lymphoma patients prior to autologous stem cell transplant: A trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood, 2016, 128: 1109.Garcia-Sanz R, Sureda A, Gonzalez A, De la Cruz F, Sanchez-Gonzalez B et al. Brentuximab Vedotin plus ESHAP (BRESHAP) is a highly effective combination for inducing remission in refractory and relapsed Hodgkin lymphoma patients prior to autologous stem cell transplant: A trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood, 2016, 128: 1109.LaCasce AS, Bociek RG, Sawas A, Caimi P, Agura E, Matous J, Ansell SM, Crosswell HE, IslasOhlmayer M, Behler C, Cheung E, Forero-Torres A, Vose J, O’Connor OA, Josephson N, Wang Y, Advani R. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood, 2018 Jul 5, 132(1): 40-48.LaCasce AS, Bociek RG, Sawas A, Caimi P, Agura E, Matous J, Ansell SM, Crosswell HE, IslasOhlmayer M, Behler C, Cheung E, Forero-Torres A, Vose J, O’Connor OA, Josephson N, Wang Y, Advani R. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood, 2018 Jul 5, 132(1): 40-48.Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J et al. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin’s lymphoma: a non-randomised open-label, single-centre, phase 2 study. Lancet Oncol, 2015 Mar, 16(3): 284-92.Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J et al. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin’s lymphoma: a non-randomised open-label, single-centre, phase 2 study. Lancet Oncol, 2015 Mar, 16(3): 284-92.Muller P, Martin K, Theurich S, Schreiner J, Savic S, Terszowski G et al. Microtubuledepolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol Res, 2014, 2: 741–755.Muller P, Martin K, Theurich S, Schreiner J, Savic S, Terszowski G et al. Microtubuledepolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol Res, 2014, 2: 741–755.Herrera A, Moskowitz A, Bartlett N, Vose J, Ramchandren R et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2017, 10: 811224.Herrera A, Moskowitz A, Bartlett N, Vose J, Ramchandren R et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2017, 10: 811224.Rothe A, Sasse S, Topp MS, et al. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2015, 125: 4024-4031.Rothe A, Sasse S, Topp MS, et al. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2015, 125: 4024-4031.Wang CM, Wu ZQ, Wang Y, et al. Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res, 2017, 23: 1156-1166.Wang CM, Wu ZQ, Wang Y, et al. Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res, 2017, 23: 1156-1166.

The authors declare that there are no conflicts of interest present.