Immunotherapy in Hodgkin lymphoma

Current and evolving roles

Authors

  • John Kuruvilla, MD, FRCPC

DOI:

https://doi.org/10.58931/cht.2022.1211

Abstract

Classical Hodgkin lymphoma (cHL) is a very curable form of cancer for the majority of patients that receive standard primary therapy. Many patients will have a second opportunity for cure at the time of first progression using approaches that incorporate high dose chemotherapy and autologous stem cell transplant (ASCT). In the non-curative setting, a group of patients (including patients with advanced age and comorbidities precluding standard therapy approaches and those with lymphoma that persists despite these treatments) will be treated with palliative intent. While these patients have had limited options in the past, novel therapies have rapidly become the standard of care in this setting. Antibodies targeting CD30 (the antibody drug conjugate brentuximab vedotin [BV]) and the immune checkpoint through PD1 (nivolumab and pembrolizumab) have now become standard approved treatments for patients beyond second-line treatment. The biology of PD1 appears particularly relevant in cHL, providing a strong clinical rationale for evaluating these agents in this malignancy. Clinicians in Canada now have several choices when making treatment decisions in patients with relapsed or refractory cHL (RR-cHL). Prospective trials are now determining the role of anti-PD1 antibodies in the curative setting.

Author Biography

John Kuruvilla, MD, FRCPC

Dr. John Kuruvilla is a Professor of Medicine at the University of Toronto and a hematologist in the Division of Medical Oncology and Hematology at the Princess Margaret Cancer Centre in Toronto. He is a member of the Lymphoma, Autologous Transplant and Immune Effector Cell Therapy programs. Dr. Kuruvilla’s research interest is the development of novel therapeutics in lymphoid malignancies and incorporating translational research into clinical trials. He is the Lymphoma Co-Chair for the Canadian Cancer Trials Group (CCTG) as well as the Chair of the Scientific Advisory Board of Lymphoma Canada.

References

Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med 2016;374:2419-29. DOI: https://doi.org/10.1056/NEJMoa1510093

Arai S, Fanale M, Devos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leukemia & Lymphoma 2013;54:2531-3. DOI: https://doi.org/10.3109/10428194.2013.798868

Fermé C, Mounier N, Diviné M, et al. Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des Lymphomes de l’Adulte H89 Trial. Journal of Clinical Oncology 2002;20:467-75. DOI: https://doi.org/10.1200/JCO.2002.20.2.467

Green MR, 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. Clinical Cancer Research 2012;18:1611-8. DOI: https://doi.org/10.1158/1078-0432.CCR-11-1942

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;372:311-9. DOI: https://doi.org/10.1056/NEJMoa1411087

Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. Journal of Clinical Oncology 2016;34:3733. DOI: https://doi.org/10.1200/JCO.2016.67.3467

Timmerman JM, Engert A, Younes A, et al. Checkmate 205 Update with Minimum 12-Month Follow up: A Phase 2 Study of Nivolumab in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma. Blood 2016;128:1110. DOI: https://doi.org/10.1182/blood.V128.22.1110.1110

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;17:1283-94. DOI: https://doi.org/10.1016/S1470-2045(16)30167-X

Zinzani PL, Engert A, Younes A, et al. Checkmate 205 Cohort C: Nivolumab in patients with classical Hodgkin lymphoma after prior brentuximab vedotin and autologous hematopoetic stem cell transplantation. Haematologica 2016;101:43-4.

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;36:1428-39. DOI: https://doi.org/10.1200/JCO.2017.76.0793

Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35:2125. DOI: https://doi.org/10.1200/JCO.2016.72.1316

Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019;134:1144-53. DOI: https://doi.org/10.1182/blood.2019000324

von Tresckow B, Fanale M, Ardeshna KM, et al. Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. Leukemia & Lymphoma. 2019. DOI: https://doi.org/10.1080/10428194.2019.1602262

Zinzani PL, Ramchandren R, Santoro A, et al. Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study. Blood. 2020;136:19-20. DOI: https://doi.org/10.1182/blood-2020-139416

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;378:331-44. DOI: https://doi.org/10.1056/NEJMoa1708984

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;385:1853-62. DOI: https://doi.org/10.1016/S0140-6736(15)60165-9

Advani RH, Moskowitz AJ, Bartlett NL, et al. Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results. Blood. 2021;138:427-38. DOI: https://doi.org/10.1182/blood.2020009178

Mei MG, Lee HJ, Palmer J, et al. Response-adapted anti-PD1 based salvage therapy for Hodgkin lymphoma with nivolumab +/- ICE (NICE). Blood. 2022. DOI: https://doi.org/10.1182/blood.2022015423

Kuruvilla J, Keating A, Crump M. How I treat relapsed and refractory Hodgkin lymphoma. Blood. 2011;117:4208-17. DOI: https://doi.org/10.1182/blood-2010-09-288373

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;14:1762-7. DOI: https://doi.org/10.1093/annonc/mdg496

Moskowitz AJ, Shah G, Schöder 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 Oct 1;39(28):3109-3117. doi:10.1200/JCO.21.01056 DOI: https://doi.org/10.1200/JCO.21.01056

Brockelmann PJ, Goergen H, Keller U, et al. Efficacy of Nivolumab and AVD in Early-Stage Unfavorable Classic Hodgkin Lymphoma: The Randomized Phase 2 German Hodgkin Study Group NIVAHL Trial. JAMA Oncol. 2020. DOI: https://doi.org/10.1001/jamaoncol.2020.0750

Ramchandren R, Domingo-Domenech E, Rueda A, et al. Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. J Clin Oncol. 2019;37:1997-2007. DOI: https://doi.org/10.1200/JCO.19.00315

Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced stage classical Hodgkin lymphoma. Blood. 2020. DOI: https://doi.org/10.1182/blood.2020007400

Cheson BD, Bartlett NL, LaPlant B, et al. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020;7:e808-e15. DOI: https://doi.org/10.1016/S2352-3026(20)30275-1

Published

2022-07-01

How to Cite

1.
Kuruvilla J. Immunotherapy in Hodgkin lymphoma: Current and evolving roles. Can Hematol Today [Internet]. 2022 Jul. 1 [cited 2024 Apr. 18];1(2):8–12. Available from: https://canadianhematologytoday.com/article/view/1-2-1-kuruvilla

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