ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 16 No. 3 (2023), BONE MARROW TRANSPLANTATION
Vol. 16 No. 3 (2023)
BONE MARROW TRANSPLANTATION

Nivo-BeGEV as Preparation for Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Classical Hodgkin Lymphoma: Results of a Multi-Center Prospective Clinical Study

Published 20.02.2024
Yana Konstantinovna Mangasarova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
T.N. Moiseeva
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
O.V. Margolin
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
L.G. Gorenkova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.S. Nesterova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
F.E. Babaeva
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
M.O. Bagova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.A. Fastova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
R.R. Abdurashidova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
L.S. Al-Radi
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.I. Dorokhina
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.M. Volodicheva
Tula Regional Clinical Hospital, 1A korp. 1 Yablochkova ul., Tula, Russian Federation, 300053
V.A. Lapin
Regional Clinical Hospital, 7 Yakovlevskaya ul., Yaroslavl, Russian Federation, 150062
O.S. Samoilova
NA Semashko Nizhny Novgorod Regional Clinical Hospital, 190 Rodionova ul., Nizhny Novgorod, Russian Federation, 603126
S.K. Kravchenko
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
A.U. Magomedova
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
E.E. Zvonkov
National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167
2023-3
PDF_2023-16-3_280-286 (Russian)

Keywords

classical Hodgkin lymphoma
Nivo-BeGEV immunochemotherapy
autologous hematopoietic stem cell transplantation
immune checkpoint inhibitors
relapse
refractory course

How to Cite

Mangasarova Y.K., Moiseeva T.N., Margolin O.V., Gorenkova L.G., Nesterova E.S., Babaeva F.E., Bagova M.O., Fastova E.A., Abdurashidova R.R., Al-Radi L.S., Dorokhina E.I., Volodicheva E.M., Lapin V.A., Samoilova O.S., Kravchenko S.K., Magomedova A.U., Zvonkov E.E. Nivo-BeGEV as Preparation for Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Classical Hodgkin Lymphoma: Results of a Multi-Center Prospective Clinical Study. Clinical Oncohematology. 2024;(3):280–286. doi:10.21320/2500-2139-2023-16-3-280-286.
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver AMA ГОСТ

Download Citation

Endnote/Zotero/Mendeley (RIS) BibTeX

Keywords

Abstract

Aim. To assess efficacy and safety of the Nivo-BeGEV (nivolumab combined with bendamustine, gemcitabine, and vinorelbine) immunochemotherapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) selected as candidates for autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. During 2018–2022, the study enrolled 51 r/r cHL patients treated with the Nivo-BeGEV immunochemotherapy. The median age was 38 years (range 19–57 years). There were 30 men and 21 women. PET-CT was performed to assess the response according to the LYRIC criteria. Safety and tolerability were analyzed by registering adverse events in line with the NCI CTCAE criteria, version 5.

Results. The median follow-up was 12 months (range 3–54 months). Complete remissions were reported in 100 % of cases. An early relapse was observed in 1 (2 %) patient. The 2-year overall and progression-free survivals were 100 % and 93 %, respectively. During Nivo-BeGEV administration, severe adverse events of grade 3/4 developed in 6 (13 %) out of 51 patients.

Conclusion. The results of this multi-center prospective clinical study of the Nivo-BeGEV immunochemotherapy used as preparation for auto-HSCT in r/r cHL patients showed high efficacy irrespective of prior drug chemotherapy and its duration with an acceptable toxicity profile.

PDF_2023-16-3_280-286 (Russian)

References

  1. Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med. 2003;348(24):2386–95. doi: 10.1056/NEJMoa022473.
  2. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet. 2002;359(9323):2065–71. doi: 10.1016/S0140-6736(02)08938-9.
  3. Moskowitz CH, Yahalom J, Zelenetz AD, et al. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  4. Labrador J, Cabrero-Calvo M, Perez-Lopez E, et al. ESHAP as salvage therapy for relapsed or refractory Hodgkin’s lymphoma. Ann Hematol. 2014;93(10):1745–53. doi: 10.1007/s00277-014-2114-0.
  5. Josting A, Muller H, Borchmann P, et al. Dose intensity of chemotherapy in patients with relapsed Hodgkin’s lymphoma. J Clin Oncol. 2010;28(34):5074–80. doi: 10.1200/JCO.2010.30.5771.
  6. Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica. 2007;92(1):35–41. doi: 10.3324/haematol.10661.
  7. Santoro A, Mazza R, Pulsoni A, et al. Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma. Blood Adv. 2020;4(1):136–40. doi: 10.1182/bloodadvances.2019000984.
  8. Baetz T, Belch A, Couban S, et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 2003;14(12):1762–7. doi: 10.1093/annonc/mdg496.
  9. Armand P, Shipp MA, 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):3733–9. doi: 10.1200/JCO.2016.67.3467.
  10. Armand P, 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. doi: 10.1200/JCO.2017.76.0793.
  11. Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019;134(14):1144–53. doi: 10.1182/blood.2019000324.
  12. Лепик К.В., Волков Н.П., Михайлова Н.Б. и др. Отдаленные результаты терапии ниволумабом у пациентов с рецидивами и рефрактерным течением классической лимфомы Ходжкина после высокодозной химиотерапии с трансплантацией аутологичных гемопоэтических стволовых клеток в реальной клинической практике. Клиническая онкогематология. 2020;13(3):280–8. doi: 10.21320/2500-2139-2020-13-3-280-288.
  13. [Lepik KV, Volkov NP, Mikhailova NB, et al. Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice. Clinical oncohematology. 2020;13(3):280–8. doi: 10.21320/2500-2139-2020-13-3-280-288. (In Russ)]
  14. Moskowitz AJ, Schoder H, Yahalom 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;16(3):284–92. doi: 10.1016/S1470-2045(15)70013-6.
  15. Moskowitz AJ, Advani RH, Bartlett NL, et al. Brentuximab Vedotin and Nivolumab for Relapsed or Refractory Classic Hodgkin Lymphoma: Long-Term Follow-up Results from the Single-Arm Phase 1/2 Study. Blood. 2019;134(Suppl_1):238. doi: 10.1182/blood-2019-122576.
  16. Gusak A, Fedorova L, Lepik K, et al. Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations. Cancers (Basel). 2021;13(22):5676. doi: 10.3390/cancers13225676.
  17. Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol. 2016;34(23):2690–7. doi: 10.1200/JCO.2016.66.4482.
  18. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9. doi: 10.1056/NEJMoa1411087.
  19. Carreau NA, Pail O, Armand P, et al. Checkpoint Blockade Treatment May Sensitize Hodgkin Lymphoma to Subsequent Therapy. Oncologist. 2020;25(10):878–85. doi: 10.1634/theoncologist.2020-0167.
  20. Rossi C, Gilhodes J, Maerevoet M, et al. Efficacy of chemotherapy or chemo-anti-PD-1 combination after failed anti-PD-1 therapy for relapsed and refractory Hodgkin lymphoma: A series from Lysa centers. Am J Hematol. 2018;93(8):1042–9. doi: 10.1002/ajh.25154.
  21. Mocikova H, Pytlik R, Markova J, et al. Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma. Leuk Lymphoma. 2011;52(9):1668–74. doi: 10.3109/10428194.2011.573889.
  22. Smeltzer JP, Cashen AF, Zhang Q, et al. Prognostic significance of FDG-PET in relapsed or refractory classical Hodgkin lymphoma treated with standard salvage chemotherapy and autologous stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(11):1646–52. doi: 10.1016/j.bbmt.2011.04.011.
  23. Devillier R, Coso D, Castagna L, et al. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy. Haematologica. 2012;97(7):1073–9. doi: 10.3324/haematol.2011.056051.
  24. Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood. 2012;119(7):1665–70. doi: 10.1182/blood-2011-10-388058.
  25. Gentzler RD, Evens AM, Rademaker AW, et al. F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma. Br J Haematol. 2014;165(6):793–800. doi: 10.1111/bjh.12824.
  26. Cheson BD, Ansell S, Schwartz L, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016;128(21):2489–96. doi: 10.1182/blood-2016-05-718528.
  27. Moskowitz AJ, Shah G, Schoder H, et al. Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2021;39(28):3109–17. doi: 10.1200/JCO.21.01056.
  28. Mei MG, Lee HJ, Palmer JM, et al. Response-adapted anti-PD-1–based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE. Blood. 2022;139(25):3605–16. doi: 10.1182/blood.2022015423.
  29. Bryan LJ, Casulo C, Allen P, et al. Pembrolizumab (PEM) Added to ICE Chemotherapy Results in High Complete Metabolic Response Rates in Relapsed/Refractory Classic Hodgkin Lymphoma (cHL): A Multi-Institutional Phase II Trial. Blood. 2021;138(Suppl 1):229. doi: 10.1182/blood-2021-145111.
  30. Мамедова А.А., Мочкин Н.Е., Саржевский В.О. и др. Комбинированная иммунохимиотерапия у больных рефрактерной/рецидивирующей классической лимфомой Ходжкина как лечение 2-й линии перед аутологичной трансплантацией кроветворных стволовых клеток (предварительные результаты). Онкогематология. 2022;17(3):40–7. doi: 10.17650/1818-8346-2022-17-3-40-47.
  31. [Mamedova AA, Mochkin NE, Sarzhevskiy VO, et al. Combined immunochemotherapy in patients with refractory/relapsed classical Hodgkin’s lymphoma as a 2nd line treatment before autologous hematopoietic stem cell transplantation (preliminary results). Oncohematology. 2022;17(3):40–7. doi: 10.17650/1818-8346-2022-17-3-40-47. (In Russ)]
  32. Moskowitz CH, Nademanee 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, placebo-controlled, phase 3 trial. Lancet. 2015;385(9980):1853–62. doi: 10.1016/S0140-6736(15)60165-9.
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.