Skip to main content
SpringerLink
Log in

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective “real-life” analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2–11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47–0.68) and 78.7% (95% CI, 0.68–0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA (1992) Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327(21):1478–1484. https://doi.org/10.1056/NEJM199211193272102

    Article  CAS  PubMed  Google Scholar 

  2. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM, Michelangelo F, Gruppo Italiano di Terapie Innovative nei L, Intergruppo Italiano L (2011) ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med 365(3):203–212. https://doi.org/10.1056/NEJMoa1100340

    Article  CAS  PubMed  Google Scholar 

  3. Borchmann P, Haverkamp H, Lohri A, Mey U, Kreissl S, Greil R, Markova J, Feuring-Buske M, Meissner J, Duhrsen U, Ostermann H, Keller U, Maschmeyer G, Kuhnert G, Dietlein M, Kobe C, Eich H, Baues C, Stein H, Fuchs M, Diehl V, Engert A (2017) Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin’s lymphoma treated with BEACOPPescalated alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group. The Lancet Oncology 18(4):454–463. https://doi.org/10.1016/S1470-2045(17)30103-1

    Article  CAS  PubMed  Google Scholar 

  4. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372(4):311–319. https://doi.org/10.1056/NEJMoa1411087

    Article  CAS  PubMed  Google Scholar 

  5. Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, Snyder ES, Ricart AD, Balakumaran A, Rose S, Moskowitz CH (2016) Programmed Death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. https://doi.org/10.1200/JCO.2016.67.3467

  6. Bekoz H, Karadurmus N, Paydas S, Turker A, Toptas T, Firatli Tuglular T, Sonmez M, Gulbas Z, Tekgunduz E, Kaya AH, Ozbalak M, Tastemir N, Kaynar L, Yildirim R, Karadogan I, Arat M, Pepedil Tanrikulu F, Ozkocaman V, Abali H, Turgut M, Kurt Yuksel M, Ozcan M, Dogu MH, Kabukcu Hacioglu S, Barista I, Demirkaya M, Koseoglu FD, Toprak SK, Yilmaz M, Demirkurek HC, Demirkol O, Ferhanoglu B (2017) Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Oncol 28(10):2496–2502. https://doi.org/10.1093/annonc/mdx341

    Article  CAS  PubMed  Google Scholar 

  7. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 32(27):3059–3068. https://doi.org/10.1200/JCO.2013.54.8800

    Article  Google Scholar 

  8. Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF, Armand P (2016) Refinement of the Lugano classification lymphoma response criteria in the era of immunomodulatory therapy. Blood 128(21):2489–2496. https://doi.org/10.1182/blood-2016-05-718528

    Article  CAS  PubMed  Google Scholar 

  9. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V (2007) Revised response criteria for malignant lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 25(5):579–586. https://doi.org/10.1200/JCO.2006.09.2403

    Article  Google Scholar 

  10. Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (June 14, 2010).

  11. Bair SM, Strelec L, Nagle SJ, Nasta SD, Landsburg DJ, Mato AR, Loren AW, Schuster SJ, Stadtmauer EA, Svoboda J (2017) Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after autologous stem cell transplant in the current era of novel therapeutics: a retrospective analysis. Am J Hematol 92(9):879–884. https://doi.org/10.1002/ajh.24792

    Article  CAS  PubMed  Google Scholar 

  12. Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A (2016) 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 17(9):1283–1294. https://doi.org/10.1016/S1470-2045(16)30167-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH (2017) Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology:JCO2016721316. https://doi.org/10.1200/JCO.2016.72.1316

  14. Armand P, Engert A, Younes A, Lee HJ, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Savage KJ, Kuruvilla J, Trněný M, Shipp MA, Sacchi M, Sumbul A, SM A (2018) Nivolumab for relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic cell transplantation (auto-HCT): extended follow-up of the phase 2 single-arm CheckMate 205 study. Paper presented at the American Society of Hematology 60th Annual Meeting & Exposition 2018, San Diego, CA, December 1-4, 2018

  15. Manson G, Mear JB, Herbaux C, Schiano JM, Casasnovas O, Stamatoullas A, Deau B, Schmitt A, Garnier G, Regny C, Bouabdallah K, Moles-Moreau MP, Ghesquieres H, Tempescul A, Dulery R, Nicolas-Virelizier E, Delmer A, Borel C, Chauchet A, Damotte D, Dercle L, Brice P, Houot R, Lysa (2019) Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation. Eur J Cancer 115:47-56. https://doi.org/10.1016/j.ejca.2019.04.006

  16. Martinez C, Carpio C, Heras I, Herranz ER, Buch J, Gutierrez A, Romero S, Ceberio I, Garcia-Garcia I, Izquierdo AR, Alonso R, Bargay J, Lekue CB, Javier N, de Haro ME, Palomera L, R G-S (2018) Nivolumab for heavily pretreated relapsed/refractory Hodgkin lymphoma: real-life experience in Spain (Spanish Group of Lymphoma and Bone Marrow Transplantation, GELTAMO). Paper presented at the American Society of Hematology 60th Annual Meeting & Exposition 2018, San Diego, CA, December 1-4, 2018

  17. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30(18):2183–2189. https://doi.org/10.1200/JCO.2011.38.0410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM (2018) 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 36(14):1428–1439. https://doi.org/10.1200/JCO.2017.76.0793

    Article  CAS  Google Scholar 

  19. Rossi C, Gilhodes J, Maerevoet M, Herbaux C, Morschhauser F, Brice P, Garciaz S, Borel C, Ysebaert L, Oberic L, Lazarovici J, Deau B, Dupuis J, Chauchet A, Abraham J, Bijou F, Stamatoullas-Bastard A, Malfuson JV, Golfier C, Laurent C, Pericart S, Traverse-Glehen A, Kanoun S, Filleron T, Casasnovas RO, Ghesquieres H (2018) 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. https://doi.org/10.1002/ajh.25154

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Medipol University, Istanbul, Istanbul, Turkey

    Huseyin Bekoz

  2. Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey

    Murat Ozbalak

  3. Division of Medical Oncology, Department of Internal Medicine, Gulhane Research and Training Hospital, Ankara, Turkey

    Nuri Karadurmus

  4. Division of Medical Oncology, Department of Internal Medicine, Cukurova University, Adana, Turkey

    Semra Paydas

  5. Division of Medical Oncology, Department of Internal Medicine, Hacettepe University, Ankara, Turkey

    Alev Turker & Ibrahim Barista

  6. Division of Hematology, Department of Internal Medicine, Marmara University, Istanbul, Turkey

    Tayfur Toptas & Tülin Firatli Tuglular

  7. Division of Hematology, Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Ankara, Turkey

    Fevzi Altuntas & Merih Kizil Cakar

  8. Division of Hematology, Department of Internal Medicine, Karadeniz Technical University, Trabzon, Turkey

    Mehmet Sonmez

  9. Division of Hematology, Anadolu Medical Center, Izmıt, Turkey

    Zafer Gulbas

  10. Division of Hematology, Department of Internal Medicine, Gazi Yasargil Research and Training Hospital, Diyarbakir, Turkey

    Nazlı Demir

  11. Division of Hematology, Department of Internal Medicine, Erciyes University, Kayseri, Turkey

    Leylagul Kaynar

  12. Division of Hematology, Department of Internal Medicine, Ataturk University, Erzurum, Turkey

    Rahsan Yildirim

  13. Division of Hematology, Medstar Antalya Hospital, Antalya, Turkey

    Ihsan Karadogan

  14. Division of Hematology, Florence Nighthingale Hospital, Istanbul, Turkey

    Mutlu Arat

  15. Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey

    Irem Kapucu

  16. Division of Hematology, Dr. Ersin Arslan Research and Training Center, Gaziantep, Turkey

    Nevin Alayvaz Aslan

  17. Division of Hematology, Department of Internal Medicine, Uludag University, Bursa, Turkey

    Vildan Ozkocaman

  18. Division of Hematology, Department of Internal Medicine, Ondokuz Mayıs University, Samsun, Turkey

    Mehmet Turgut

  19. Division of Hematology, Department of Internal Medicine, Ankara University, Ankara, Turkey

    Meltem Kurt Yuksel, Muhit Ozcan & Selami K. Toprak

  20. Division of Hematology, Department of Internal Medicine, Pamukkale University, Denizli, Turkey

    Sibel Kabukcu Hacioglu

  21. Division of Medical Oncology, Department of Pediatrics, Uludag University, Bursa, Turkey

    Metin Demirkaya

  22. Division of Hematology, Department of Internal Medicine, Ege University, Izmir, Turkey

    Guray Saydam

  23. Division of Hematology, Department of Internal Medicine, Gaziantep University, Gaziantep, Turkey

    Mehmet Yilmaz

  24. Department of Nuclear Medicine, Koc University School of Medicine, İstanbul, Turkey

    Onur Demirkol

  25. Division of Hematology, Department of Internal Medicine, Koc University School of Medicine and V.K.V. American Hospital, İstanbul, Turkey

    Burhan Ferhanoglu

Authors
  1. Huseyin Bekoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murat Ozbalak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nuri Karadurmus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Semra Paydas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alev Turker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tayfur Toptas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tülin Firatli Tuglular
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fevzi Altuntas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Merih Kizil Cakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mehmet Sonmez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zafer Gulbas
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nazlı Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Leylagul Kaynar
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Rahsan Yildirim
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ihsan Karadogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mutlu Arat
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Irem Kapucu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Nevin Alayvaz Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Vildan Ozkocaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Mehmet Turgut
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Meltem Kurt Yuksel
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Muhit Ozcan
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Sibel Kabukcu Hacioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Ibrahim Barista
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Metin Demirkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Guray Saydam
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Selami K. Toprak
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Mehmet Yilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Onur Demirkol
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Burhan Ferhanoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.B., B.F., and M.Ozb. coordinated the study. B.F., H.B., S.P., and M.Ozb. wrote the manuscript. M.Ozb. performed the statistical evaluations. H.B., N.K., S.P., A.T., T.T., T.F.T., F.A., M.K.C., M.S., Z.G., N.D, L.K., R.Y., İ.K., M.A., N.A.A., V.O., M.T., M.K.Y., M.O., İ.K., S.K.H., I.B., M.D., G.S., S.K.T., M.Y., and B.F. contributed data. B.F. served as the principal investigator.

Corresponding author

Correspondence to Burhan Ferhanoglu.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The NPP was organized after ethical approval, with the supervision of the Ministry of Health. The study was approved by the local ethical committee.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bekoz, H., Ozbalak, M., Karadurmus, N. et al. Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Hematol 99, 2565–2576 (2020). https://doi.org/10.1007/s00277-020-04077-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-04077-4

Keywords

Search

Navigation