Future directions in Hodgkin lymphoma: checkpoint inhibitors and beyond

References

• Sasse S, Brockelmann PJ, Goergen H, et al. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017;35:1999–2007.
   PubMed Web of Science ®Google Scholar
• Casasnovas RO, Bouabdallah R, Brice P, et al. PET-guided, BEACOPPescalated therapy in advanced Hodgkin lymphoma – authors’ reply. Lancet Oncol. 2019;20:e190.
   PubMed Web of Science ®Google Scholar
• Barrington SF, Kirkwood AA, Franceschetto A, et al. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study. Blood. 2016;127:1531–1538.
   PubMed Web of Science ®Google Scholar
• Schmitz N, Pfistner B, Sextro M, et al., Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. 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;359:2065–2071.
   PubMed Web of Science ®Google Scholar
• Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet. 1993;341:1051–1054.
   PubMed Web of Science ®Google Scholar
• Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001;97:616–623.
   PubMed Web of Science ®Google Scholar
• 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;385:1853–1862.
   PubMed Web of Science ®Google Scholar
• Shah GL, Yahalom J, Matasar MJ, et al. Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation. Br J Haematol. 2016;175:440–447.
   PubMed Web of Science ®Google Scholar
• Kaloyannidis P, Hertzberg M, Webb K, et al. Brentuximab vedotin for the treatment of patients with relapsed or refractory Hodgkin lymphoma after autologous stem cell transplantation. Br J Haematol. 2020;188:540–549.
   PubMed Web of Science ®Google Scholar
• Armand P, Chen YB, Redd RA, et al. PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation. Blood. 2019;134:22–29.
   PubMed Web of Science ®Google Scholar
• van de Donk NW, Dhimolea E. Brentuximab vedotin. MAbs. 2012;4:458–465.
   PubMed Web of Science ®Google Scholar
• Green MR, Monti S, Rodig SJ, 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;116:3268–3277.
   PubMed Web of Science ®Google Scholar
• 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;36:1428–1439.
   PubMed Web of Science ®Google Scholar
• Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019;134:1144–1153.
   PubMed Web of Science ®Google Scholar
• Shi Y, Su H, Song Y, et al. Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2019;6:e12–e19.
   PubMed Web of Science ®Google Scholar
• Song Y, Gao Q, Zhang H, et al. Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study. Leukemia. 2020;34:533–542.
   PubMed Web of Science ®Google Scholar
• Song Y, Wu J, Chen X, et al. A single-arm, multicenter, phase II study of camrelizumab in relapsed or refractory classical Hodgkin lymphoma. Clin Cancer Res. 2019;25:7363–7369.
   PubMed Web of Science ®Google Scholar
• Chen R, Gibb AL, Collins GP, et al. Blockade of the PD-1 checkpoint with anti–PD-L1 antibody avelumab is sufficient for clinical activity in relapsed/refractory classical hodgkin lymphoma (CHL). Hematol Oncol. 2017;35:67.
   PubMedGoogle Scholar
• Younes A, Gopal AK, Smith SE, 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.
   PubMed Web of Science ®Google Scholar
• Kuruvilla J, Ramchandren R, Santoro A, et al. KEYNOTE-204: randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL). J Clin Oncol. 2020;38:8005–8005.
   Web of Science ®Google Scholar
• 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;16:284–292.
   PubMed Web of Science ®Google Scholar
• LaCasce AS, Bociek RG, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018;132:40–48.
   PubMed Web of Science ®Google Scholar
• Herrera AF, Moskowitz AJ, Bartlett NL, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131:1183–1194.
   PubMed Web of Science ®Google Scholar
• Moskowitz CH, Walewski J, Nademanee A, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132:2639–2642.
   PubMed Web of Science ®Google Scholar
• Connors JM, Radford JA. Brentuximab vedotin for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:1560–1561.
   PubMedGoogle Scholar
• Connors JM, Jurczak W, Straus DJ, Ansell SM, et al., ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331–344.
   PubMed Web of Science ®Google Scholar
• Park SI, Shea TC, Olajide O, et al. ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma. Blood Adv. 2020;4:2548–2555.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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;6:872–880.
   PubMed Web of Science ®Google Scholar
• Allen PB, Savas H, Evens AM, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced stage classical Hodgkin lymphoma. Blood. 2020.
   Web of Science ®Google Scholar
• Yasenchak CA, Bordoni R, Yazbeck V, et al. Phase 2 study of frontline brentuximab vedotin plus nivolumab in patients with Hodgkin lymphoma aged ≥60 years. Blood. 2019;134:237–237.
   Web of Science ®Google Scholar
• 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–e815.
   PubMed Web of Science ®Google Scholar
• Armand P, Lesokhin A, Borrello I, et al. A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Leukemia. 2020.
   Web of Science ®Google Scholar
• Diefenbach CS, Hong F, Ambinder RF, et al. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020;7:e660–e670.
   PubMed Web of Science ®Google Scholar
• Zhang H, Deng M, Lin P, et al. Frontiers and opportunities: highlights of the 2(nd) Annual Conference of the Chinese Antibody Society. Antib Ther. 2018;1:65–74.
   PubMedGoogle Scholar
• Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28:543.
   PubMed Web of Science ®Google Scholar
• Nie J, Wang C, Liu Y, et al. Addition of low-dose decitabine to anti-PD-1 antibody camrelizumab in relapsed/refractory classical hodgkin lymphoma. J Clin Oncol. 2019;37:1479–1489.
   PubMed Web of Science ®Google Scholar
• Gattringer G, Greil R, Radaszkiewicz T, et al. In situ quantification of T-cell subsets, NK-like cells and macrophages in Hodgkin’s disease: quantity and quality of infiltration density depends on histopathological subtypes. Blut. 1986;53:49–58.
   PubMedGoogle Scholar
• Al Sam S, Jones DB, Payne SV, et al. Natural killer (NK) activity in the spleen of patients with Hodgkin’s disease and controls. Br J Cancer. 1982;46:806–810.
   PubMed Web of Science ®Google Scholar
• Ayoub JP, Palmer JL, Huh Y, et al. Therapeutic and prognostic implications of peripheral blood lymphopenia in patients with Hodgkin’s disease. Leuk Lymphoma. 1999;34:519–527.
   PubMed Web of Science ®Google Scholar
• Tursz T, Dokhelar MC, Lipinski M, et al. Low natural killer cell activity in patients with malignant lymphoma. Cancer. 1982;50:2333–2335.
   PubMed Web of Science ®Google Scholar
• Alvaro-Naranjo T, Lejeune M, Salvado-Usach MT, et al. Tumor-infiltrating cells as a prognostic factor in Hodgkin’s lymphoma: a quantitative tissue microarray study in a large retrospective cohort of 267 patients. Leuk Lymphoma. 2005;46:1581–1591.
   PubMed Web of Science ®Google Scholar
• Croop JM, Cooper R, Fernandez C, et al. Mobilization and collection of peripheral blood CD34+ cells from patients with Fanconi anemia. Blood. 2001;98:2917–2921.
   PubMedGoogle Scholar
• Lopez-Verges S, Milush JM, Pandey S, et al. CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood. 2010;116:3865–3874.
   PubMed Web of Science ®Google Scholar
• Chiu J, Ernst DM, Keating A. Acquired natural killer cell dysfunction in the tumor microenvironment of classic Hodgkin lymphoma. Front Immunol. 2018;9:267.
   PubMed Web of Science ®Google Scholar
• Reiners KS, Kessler J, Sauer M, et al. Rescue of impaired NK cell activity in hodgkin lymphoma with bispecific antibodies in vitro and in patients. Mol Ther. 2013;21:895–903.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Bartlett NL, Herrera AF, Domingo-Domenech E, et al. A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2020;136:2401–2409.
   PubMed Web of Science ®Google Scholar
• June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73.
   PubMed Web of Science ®Google Scholar
• Brocker T, Peter A, Traunecker A, et al. New simplified molecular design for functional T cell receptor. Eur J Immunol. 1993;23:1435–1439.
   PubMed Web of Science ®Google Scholar
• Krause A, Guo HF, Latouche JB, et al. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998;188:619–626.
   PubMed Web of Science ®Google Scholar
• Sadelain M, Brentjens R, Riviere I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009;21:215–223.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–2544.
   PubMed Web of Science ®Google Scholar
• Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–448.
   PubMed Web of Science ®Google Scholar
• Bollard CM, Gottschalk S, Torrano V, et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014;32:798–808.
   PubMed Web of Science ®Google Scholar
• Dotti G, Gottschalk S, Savoldo B, et al. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257:107–126.
   PubMed Web of Science ®Google Scholar
• Nijland M, Veenstra RN, Visser L, et al. HLA dependent immune escape mechanisms in B-cell lymphomas: implications for immune checkpoint inhibitor therapy? Oncoimmunology. 2017;6:e1295202.
   PubMed Web of Science ®Google Scholar
• van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin’s lymphoma. Am J Pathol. 1999;154:1685–1691.
   PubMed Web of Science ®Google Scholar
• Ishida T, Ishii T, Inagaki A, et al. Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res. 2006;66:5716–5722.
   PubMed Web of Science ®Google Scholar
• Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362:875–885.
   PubMed Web of Science ®Google Scholar
• Turtle CJ, Hanafi LA, Berger C, et al. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8:355ra116.
   PubMed Web of Science ®Google Scholar
• Ramos CA, Ballard B, Zhang H, et al. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017;127:3462–3471.
   PubMed Web of Science ®Google Scholar
• Wang D, Zeng C, Xu B, et al. Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients. Blood Cancer J. 2020;10:8.
   PubMed Web of Science ®Google Scholar
• Ramos CA, Bilgi M, Gerken C, et al. CD30-chimeric antigen receptor (CAR) T cells for therapy of Hodgkin lymphoma (HL). Biol Blood Marrow Transplant. 2019;25:S63.
   PubMed Web of Science ®Google Scholar
• Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2020;38:3794–3804.
   PubMed Web of Science ®Google Scholar
• Burchill MA, Yang J, Vang KB, et al. Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol Lett. 2007;114:1–8.
   PubMed Web of Science ®Google Scholar
• Malek TR, Yu A, Vincek V, et al. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity. 2002;17:167–178.
   PubMed Web of Science ®Google Scholar
• Almeida AR, Legrand N, Papiernik M, et al. Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J Immunol. 2002;169:4850–4860.
   PubMed Web of Science ®Google Scholar
• Re D, Kuppers R, Diehl V. Molecular pathogenesis of Hodgkin’s lymphoma. J Clin Oncol. 2005;23:6379–6386.
   PubMed Web of Science ®Google Scholar
• Hartley JA. The development of pyrrolobenzodiazepines as antitumour agents. Expert Opin Investig Drugs. 2011;20:733–744.
   PubMed Web of Science ®Google Scholar
• Flynn MJ, Zammarchi F, Tyrer PC, et al. ADCT-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Mol Cancer Ther. 2016;15:2709–2721.
   PubMed Web of Science ®Google Scholar
• Flynn MJ, Hartley JA. The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer. Br J Haematol. 2017;179:20–35.
   PubMed Web of Science ®Google Scholar
• Hamadani M, Collins GP, Samaniego F, et al. Phase 1 study of Adct-301 (camidanlumab tesirine), a novel pyrrolobenzodiazepine-based antibody drug conjugate, in relapsed/refractory classical Hodgkin lymphoma. Blood. 2018;132:928–928.
   Web of Science ®Google Scholar