Иммунотерапия классической лимфомы Ходжкина


Цитировать

Полный текст

Открытый доступ Открытый доступ
Доступ закрыт Доступ предоставлен
Доступ закрыт Доступ платный или только для подписчиков

Аннотация

Высокодозная химиотерапия с аутологичной трансплантацией гемопоэтических стволовых клеток (ВДХТ с аутоТГСК) служит современным стандартом лечения первично рефрактерных форм и первых рецидивов лимфомы Ходжкина (ЛХ). ВДХТ с аутоТГСК эффективна для 50-60% пациентов при первом позднем химиочувствительном рецидиве ЛХ. Современные методы терапии лечения ЛХ. с высокой эффективностью и низкой токсичностью особенно актуальны для пациентов с ЛХ, которые не являются кандидатами для ВДХТ с аутоТГСК, а также при возникновении рецидивов ЛХ. после ВДХТ с аутоТГСК. Аллогенные трансплантации гемопоэтических стволовых клеток (аллоТГСК) могут проводиться при рецидивах ЛХ. после ВДХТ с аутоТГСК с сохраненной химиочувствительностью, предпочтительно для молодых пациентов в рамках проспективных клинических исследований. Брентуксимаб ведотин зарегистрирован для лечения пациентов с классической ЛХпосле неудачи (прогрессирование или ранний рецидив) ВДХТ с аутоТГСК или пациентов - не кандидатов для ВДХТ с аутоТГСК, при неудаче двух и более линий химиотерапии (ХТ), для консолидации после ВДХТ с аутоТГСК у пациентов с ЛХ. с высоким риском возникновения рецидива или прогрессирования, в терапии первой линии при распространенных стадиях ЛХ, наиболее предпочтительно для молодых пациентов, пациентов с высоким риском возникновения рецидива. Высокая активность отмечена у ингибиторов контрольных точек PD-1/PD-L1, активирующих противоопухолевый иммунитет (ниволумаб, пембролизумаб), у пациентов с рецидивами ЛХ. Терапевтическая эффективность ингибиторов контрольных точек PD-1/PD-L1 не зависит от ответа на предшествовавшие режимы терапии (первичная рефрактерность или рефрактерность к брентуксимабу ведотину). Перспективные направления терапии ЛХ. связаны с дальнейшим изучением новых мишеней опухолевых клеток и их сигнальных путей.

Полный текст

Доступ закрыт

Об авторах

Л. В Филатова

Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова; Северо-Западный государственный медицинский университет им. И.И. Мечникова

Email: Larisa_Filatova@list.ru
д.м.н., ведущий науч. сотр. научного отдела инновационных методов терапевтической онкологии и реабилитации; доцент кафедры онкологии 197758, Россия, Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

Список литературы

  1. Diehl V., Franklin J., Pfreundschuh M., Lathan B., et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003;348:2386-95. doi: 10.1056/NEJMoa022473.
  2. Engert A., Diehl V., Franklin J., et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 2009, 27:454854. doi: 10.1200/JCO.2008.19.8820.
  3. Armttage J.O. Early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363:653-62. doi: 10.1056/NEJMra1003733
  4. Schmitz N, Pfistner B, Sextro M., et al. Aggressive conventional chemotherapy compared with highdose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomized trial. Lancet. 2002;359:2065-71. doi: 10.1016/S0140-6736(02)08938-9.
  5. Majhail N.S., Weisdorf D.J., Defor T.E., et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma. Biol Blood Marrow Transplant. 2006;12:1065-72. doi: 10.1016/j.bbmt.2006.06.006.
  6. Sureda A., Constans M., Iriondo A., et al. Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse. Ann Oncol. 2005;16:625-33. doi: 10.1093/annonc/mdi119
  7. Horning S.J., Chao N.J., Negrin R.S, et al. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices. Blood. 1997;89:801-13.
  8. Lavoie J.C., Connors J.M., Phillips G.L., et al. High-dose therapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood. 2005;106:1473-78. doi: 10.1182/blood-2004-12-4689.
  9. Gerrie A.S., Power M.M., Shepherd J.D., et al. Chemoresistance can be overcome with highdose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Ann Oncol. 2014;25:2218-23. doi: 10.1093/annonc/mdu387.
  10. Arai S., Fanale M., DeVos S., et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54(11):2531-33. doi: 10.3109/10428194.2013.798868.
  11. Reyal Y., Kayani I., Bloor A.J., et al. Impact of pretransplantation (18)F-fluorodeoxyglucose-positron emission tomography on survival outcomes after T cell-depleted allogeneic transplantation for Hodgkin lymphoma. Biol Blood Marrow Transplant. 2016;22(7):1234-41. doi: 10.1016/j.bbmt.2016.03.034
  12. Farina L., Castagna L., Farina L., et al. Allogeneic transplantation improves the overall and progressionfree survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115:3671-77. doi: 10.1182/blood-2009-12-253856.
  13. Thomson K.J., Peggs K.S., Smith P., et al. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation. Bone Marrow Transplant. 2008;41(9):765-70. doi: 10.1038/sj.bmt.1705977.
  14. Sarina B., Castagna L., Farina L., et al; Gruppo Italiano Trapianto di Midollo Osseo. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115(18): 3671-77. Doi: 10.1182/ blood-2009-12-253856.
  15. Younes A, Bartlett N.L., LeonardJ.P., et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1112-21. doi: 10.1056/NEJMoa1002965.
  16. Fanale M.A., Forero-Torres A., Rosenblatt J.D., et al. A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive Hematologic Malignancies. Clin Cancer Res. 2012;18:248-55. doi: 10.1158/1078-0432.CCR-11-1425.
  17. Younes A., Gopal A.K., Smith S.E., 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;30:2183-89. doi: 10.1200/JCO.2011.38.0410.
  18. Gopal A.K., Chen R., Smith S.E., et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125:1236-43. doi: 10.1182/blood-2014-08-595801.
  19. Chen R., Gopal A.K., Smith S.E., et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016; 128(12):1562-66. doi: 10.1182/blood-2016-02-699850.
  20. Perrot A., Monjanel H., Bouabdallah R., et al. Lymphoma Study Association (LYSA). Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program. Haematologica. 2016;101:466-73. doi: 10.3324/haematol.2015.134213.
  21. Moskowitz C.H., Nadamanee A., Masszi T., 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, placebocontrolled, phase 3 trial. Lancet. 2015;385:1853-62. doi: 10.1016/S0140-6736(15)60165-9.
  22. Moskowitz A.J., Schöder H., Gavane S., et al. Baseline metabolic tumor volume is an independent prognostic factor for relapsed and refractory Hodgkin lymphoma patients receiving PET-adapted salvage therapy with brentuximab vedotin and augmented ICE [ICML abstract 018]. Hematol Oncol. 2017;35(Suppl. S2):36-7. doi: 10.1002/hon.2437_17.
  23. Herrera A., Palmer J.M., Manin P., et al. Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Ann Oncol. 2017;29: 724-30. doi: 10.1093/annonc/mdx791.
  24. Herrera A.F., Moskowitz A.J., Bartlett N.L., et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131:1183-94. Doi: https://doi.org/10.1182/blood-2017-10-811224.
  25. LaCasce A.S., Bociek G., Sawas A., et al. Brentuximab Vedotin Plus Bendamustine: A Highly Active Salvage Treatment Regimen for Patients with Relapsed or Refractory Hodgkin Lymphoma. Blood. 2015;126(23):3982.
  26. Garcia-Sanz R., Sureda A., Gonzalez A.P., 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.
  27. Cassaday R.D., Fromm J., Cowan A.J., et al. Safety and activity of brentuximab vedotin (BV) plus ifosfamide, carboplatin, and etoposide (ICE) for rel/ref (rel/ref) classical Hodgkin lymphoma (cHL): initial results of a phase I/II trial. Blood. 2016;128:1834.
  28. Hagenbeek A., Zijlstra J., Lugtenburg P., et al. Transplant brave: combining brentuximab vedotin with DHAP as salvage treatment in rel/ref Hodgkin lymphoma. A phase 1 dose-escalation study. Haematologica. 2016;101:44.
  29. Younes A., Connors J.M., Park S.I., et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet. Oncology. 2013;14:1348-56. doi: 10.1016/S1470-2045(13)70501-1.
  30. Connors J.M., Ansell S.M., Fanale M., et al. Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma. Blood. 2017;130:1375-77. doi: 10.1182/blood-2017-05-784678.
  31. Connors J.M., Jurczak W., Staus D.J., et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018;378:331-44. doi: 10.1056/NEJMoa1708984.
  32. Eichenauer D.A., Plutxchow A., Kreissl S., et al. Incorporation of brentuximab vedotin into first-line treatment of advanced classical Hodgkin's lymphoma: final analysis of a phase 2 randomised trial by the German Hodgkin Study Group. Lancet. Oncol. 2017;18:1680-87. doi: 10.1016/S1470-2045(17)30696-4.
  33. Abramson J.S., Arnason J.E., LaCasce A.S., et al. Brentuximab vedotin plus AVD for non-bulky limited stage Hodgkin lymphoma: a phase II trial. J Clin Oncol. 2015;33(Suppl. 15):850-55.
  34. Park S.I., Olajide O., Reddy N.M., et al. Brentuximab vedotin consolidation to reduce radiation use in patients with limited stage non-bulky Hodgkin lymphoma: an update from a phase 2 clinical trial [ICML abstract 070]. Hematol Oncol. 2017; 35(Suppl. 2):81-2.
  35. Kumar A., Casulo C., Yahalom J., et al. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2016;128: 1458-64. doi: 10.1182/blood-2016-03-703470.
  36. Kumar A., Casulo C., Ranjana H., et al. A pilot study of brentuximab vedotin and AVD chemotherapy followed by 20 Gy involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2017;130(Suppl. 1):734.
  37. Evens A.M., Hong F., Gordon L.I., et al. The efficacy and tolerability of ABVD and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013;161:76-86. Doi: 10.1111/ bjh.12222.
  38. Forero-Torres A., Holkova B., Goldschmidt J., et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015;126:2798-804. doi: 10.1182/blood-2015-06-644336.
  39. Gibb A., Pirrie S., Linton K., et al. Results of a phase II study of brentuximab vedotin in the first line treatment of Hodgkin lymphoma patients considered unsuitable for standard chemotherapy (BREVITY). Hemmatol Oncol. 2017;35(Suppl. 2):80-1.
  40. Friedberg J.W., Forero-Torres A., Bordoni R.E., et al. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged 60 years with HL. Blood. 2017;130(26):2829-37. doi: 10.1182/blood-2017-06-787200.
  41. Gallamini A., Rambaldi A., Bijou F., et al. A Phase 1/2 clinical trial of brentuximab-vedotin and bendamustine in elderly patients with previously untreated advanced Hodgkin lymphoma (HALO STUDY. NCT identifier, 02467946): preliminary report. Blood. 2016;128:4154.
  42. Gallamini A, Bijou F., Viotti J., et al. Brentuximab vedotin and bendamustine is a feasible and effective drug combination as front-line treatment of Hodgkin lymphoma in the elderly (HALO TRIAL). Hematol Oncol. 2017;35(Suppl. 2):170.
  43. Evens A.M., Advani R.H., Fanale M.A., et al. Sequential brentuximab vedotin (Bv) before and after Adriamycin, Vinblastine, and Dacarbazine (Bv-AVD) for older patients with untreated Classical Hodgkin Lymphoma (cHL): final results from a multicenter phase II study. Blood. 2017:130;733.
  44. Bartlett N.L., Chen R., Fanale M., et al. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014;7:24. doi: 10.1186/1756-8722-7-24.
  45. Chen R., Hou J., Newman E., et al. CD30 Downregulation, MMAE Resistance, and MDR1 upregulation are all associated with resistance to brentuximab vedotin. Mol Cancer Ther. 2015;14:1376-84. doi: 10.1158/1535-7163. MCT-15-0036.
  46. Chen R.W, Palmer J.M., Herrera A.F., et al. Phase II study of brentuximab vedotin plus ibrutinib for patients with relapsed/refractory Hodgkin Lymphoma. Blood. 2017;130(Suppl. 1):738.
  47. O'Connor O.A., Lue J.K., Sawas A., et al. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet. Oncol. 2018;19:257-66.
  48. Diefenbach C.S., Hong F., Cohen J.B., et al. Preliminary safety and efficacy of the combination of brentuximab vedotin and ipilimumab in relapsed/refractory Hodgkin Llymphoma: a trial of the ECOG-ACRIN Cancer Research Group (E4412). Blood. 2015;126:585.
  49. Diefenbach C.S. Safety and efficacy of combination of brentuximab vedotin and nivolumab in rel/ref Hodgkin lymphoma: a trial of the ECOG-ACRIN cancer research group (E4412). Hematol Oncol. 2017;35(S2):84-5.
  50. Swaika A., Yammond W.A., Joseph R.W. Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy. Mol Immunol. 2015;67(2 Pt. А):4-17. doi: 10.1016/j.molimm.2015.02.009.
  51. Green M.R., Monti S., Rodig S.J., et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116:3268-77. doi: 10.1182/blood-2010-05-282780.
  52. Green M.R., Rodig S., Juszczynski P., et al. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: Implications for targeted therapy. Clin Cancer. Res. 2012;18:1611-18. doi: 10.1182/blood-2010-05-282780.
  53. Paydas S., Bagir E., Seydaoglu, G., et al. Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBVencoded RNA (EBER) expression in Hodgkin lymphoma. Ann Hematol. 2015;94:1545-52. doi: 10.1007/s00277-015-2403-2.
  54. Chu F., Neelapu S.S. Anti-PD-1 antibodies for the treatment of B-cell lymphoma: Importance of PD-1+ T-cellsubsets. Oncoimmunology. 2014;3(1):е28101. doi: 10.4161/onci.28101.
  55. Ansell S.M., lesokhin A.M., Borrello I., et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-19. doi: 10.1056/NEJMoa1411087.
  56. Armand F., Engert A., Younes A., et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018;36(14):1428-39.
  57. Ramchandren R., Fanale M.A., Rueda A., et al. Nivolumab for Newly Diagnosed Advanced-Stage Classical Hodgkin lymphoma (cHL): Results from the Phase 2 Checkmate 205 Study. Blood. 2017;130(Suppl. 1):651.
  58. Mahoney K.M., Freeman G.J., McDermott D.F. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015;37:764-82. doi: 10.1016/j.clinthera.2015.02.018.
  59. Armand P., Shipp M.A., Ribrag V., et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016;34(31):3733-39. doi: 10.1200/JCO.2016.67.3467.
  60. Chen R.W., Zinzani PL., Fanale M.A., et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017;35(19):2125-32.
  61. Moskowitz C.H., Zinzani P., Fanale M., et al. Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study. Blood. 2016;128:1107.
  62. Kwong Y.L., Lopes D., Khong PL. Low-dose pembrolizumab induced remission in patients with refractory classical Hodgkin lymphoma. Br J Haematol. 2017;176:131-43. doi: 10.1111/bjh.13920.
  63. Chan T.S.Y., Luk T.H., Lau J.S.M., et al. Low-dose pembrolizumab for relapsed/refractory Hodgkin lymphoma: high efficacy with minimal toxicity. Ann Hematol. 2017;96:647-51. doi: 10.1007/s00277-017-2931-z.
  64. Merryman R.W., Kim H.T., Zinzani PL., et al. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood. 2017;129(10):1380-88. doi: 10.1182/blood-2016-09-738385.
  65. Herbaux C., Gauthier J., Brice P., et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. Blood. 2017;129(18):2471-78. doi: 10.1182/blood-2016-11-749556.
  66. Haverkos B.M., Abbott D., Hamadani M., et al. PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130:221-28. doi: 10.1182/blood-2017-01-761346.
  67. Bashey A., Medina B., Corringham S., et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell ransplantation. Blood. 2009;113(7):1581-88. doi: 10.1182/blood-2008-07-168468.
  68. Davids M.S., Kim H.T., Bachireddy P., et al. Leukemia and Lymphoma Society Blood Cancer Research Partnership. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016;375(2):143-53. doi: 10.1056/NEJMoa1601202.
  69. Younes A., Santoro A., Shipp M., et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet. Oncol. 2016;17(9):1283-94. doi: 10.1016/S1470-2045(16)30167-X.
  70. Chen R., Zinzani P.L., Fanale M.A., et al. KEYNOTE-087. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125-32.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© ООО «Бионика Медиа», 2019

Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах