Current and future immunotherapeutic approaches in Hodgkin lymphoma

Leukemia and Lymphoma

Volumn 57, Issue 9, 2016, Pages 2014-2024

  Bröckelmann, Paul J ^a   Borchmann, Peter ^a   Engert, Andreas ^a  

^a UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

Author keywords

bispecific antibodies; cellular therapy; checkpoint inhibition; Hodgkin lymphoma; immunotherapy

Indexed keywords

ANTIBODY; ANTIBODY CONJUGATE; BISPECIFIC ANTIBODY; IMMUNOTOXIN; IPILIMUMAB; NIVOLUMAB; PEMBROLIZUMAB; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; TUMOR ANTIGEN; TUMOR MARKER;

ADOPTIVE IMMUNOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RECURRENCE; CELL THERAPY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SAFETY; HODGKIN DISEASE; HUMAN; NONHUMAN; PRIORITY JOURNAL; RADIOIMMUNOTHERAPY; REVIEW; TREATMENT RESPONSE; BIOLOGICAL THERAPY; GENETICS; IMMUNOTHERAPY; METABOLISM; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; PATHOLOGY; PROCEDURES; TREATMENT OUTCOME;

ANTIGENS, NEOPLASM; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; BIOMARKERS, TUMOR; CELL- AND TISSUE-BASED THERAPY; COMBINED MODALITY THERAPY; HODGKIN DISEASE; HUMANS; IMMUNOCONJUGATES; IMMUNOTHERAPY; IMMUNOTOXINS; MOLECULAR TARGETED THERAPY; TREATMENT OUTCOME;

EID: 84979246807     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.1080/10428194.2016.1185789     Document Type: Review

References (92)

1. K.Behringer, H.Goergen, F.Hitz,. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385:1418–1427.
2. B.von Tresckow, A.Plutschow, M.Fuchs,. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012;30:907–913.
3. A.Engert, H.Haverkamp, C.Kobe,. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379:1791–1799.
4. B.von Tresckow, H.Muller, D.A.Eichenauer,. Outcome and risk factors of patients with Hodgkin Lymphoma who relapse or progress after autologous stem cell transplant. Leuk Lymphoma. 2014;55:1922–1924.
5. S.Arai, M.Fanale, S.DeVos,. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013;54:2531–2533.
6. S.Sasse, B.Klimm, H.Gorgen,. Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012;23:2953–2959.
7. K.Behringer, H.Mueller, H.Goergen,. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol. 2013;31:231–239.
8. K.Behringer, A.Josting, P.Schiller,. Solid tumors in patients treated for Hodgkin's disease: a report from the German Hodgkin Lymphoma Study Group. Ann Oncol. 2004;15:1079–1085.
9. D.A.Eichenauer, I.Thielen, H.Haverkamp,. Therapy-related acute myeloid leukemia and myelodysplastic syndromes in patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2014;123:1658–1664.
10. P.Hanly, I.Soerjomataram, L.Sharp Measuring the societal burden of cancer: the cost of lost productivity due to premature cancer-related mortality in Europe. Int J Cancer J Int Du Cancer. 2015;136:E136–E145.
11. B.Boll, H.Goergen, N.Arndt,. Relapsed Hodgkin lymphoma in older patients: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol. 2013;31:4431–4437.
12. B.Boll, H.Gorgen, M.Fuchs,. ABVD in older patients with early-stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD10 and HD11 trials. J Clin Oncol. 2013;31:1522–1529.
13. C.Steidl, J.M.Connors, R.D.Gascoyne Molecular pathogenesis of Hodgkin's lymphoma: increasing evidence of the importance of the microenvironment. J Clin Oncol. 2011;29:1812–1826.
14. U.Kapp, J.Wolf, M.Hummel,. Hodgkin's lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice. Blood. 1993;82:1247–1256.
15. H.J.Gruss, D.Hirschstein, B.Wright,. Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease. Blood. 1994;84:2305–2314.
16. A.Carbone, A.Gloghini, H.J.Gruss,. CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease. Am J Pathol. 1995;147:912–922.
17. S.Poppema, A.K.Bhan, E.L.Reinherz,. In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease. Blood. 1982;59:226–232.
18. N.A.Marshall, L.E.Christie, L.R.Munro,. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103:1755–1762.
19. M.K.Gandhi, E.Lambley, J.Duraiswamy,. Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients. Blood. 2006;108:2280–2289.
20. H.Herbst, H.D.Foss, J.Samol,. Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease. Blood. 1996;87:2918–2929.
21. C.Steidl, T.Lee, S.P.Shah,. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med. 2010;362:875–885.
22. B.Z.Qian, J.W.Pollard Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39–51.
23. J.Reichel, A.Chadburn, P.G.Rubinstein,. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015;125:1061–1072.
24. M.Challa-Malladi, Y.K.Lieu, O.Califano,. Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011;20:728–740.
25. C.Steidl, S.P.Shah, B.W.Woolcock,. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 2011;471:377–381.
26. A.Rosenwald, G.Wright, K.Leroy,. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med. 2003;198:851–862.
27. M.R.Green, S.Monti, S.J.Rodig,. 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.
28. M.R.Green, S.Rodig, P.Juszczynski,. 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;18:1611–1618.
29. R.Yamamoto, M.Nishikori, T.Kitawaki,. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood. 2008;111:3220–3224.
30. B.J.Chen, B.Chapuy, J.Ouyang,. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19:3462–3473.
31. J.M.Chemnitz, D.Eggle, J.Driesen,. RNA fingerprints provide direct evidence for the inhibitory role of TGFbeta and PD-1 on CD4+ T cells in Hodgkin lymphoma. Blood. 2007;110:3226–3233.
32. P.Greaves, A.Clear, A.Owen,. Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells. Blood. 2013;122:2856–2863.
33. P.Juszczynski, J.Ouyang, S.Monti,. The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci USA. 2007;104:13134–13139.
34. S.J.Rodig, J.Ouyang, P.Juszczynski,. AP1-dependent galectin-1 expression delineates classical Hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features. Clin Cancer Res. 2008;14:3338–3344.
35. J.Ouyang, A.Plutschow, E.Pogge von Strandmann,. Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood. 2013;121:3431–3433.
36. A.Engert, V.Diehl, R.Schnell,. A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood. 1997;89:403–410.
37. R.Schnell, O.Staak, P.Borchmann,. A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma. Clin Cancer Res. 2002;8:1779–1786.
38. R.Schnell, E.Vitetta, J.Schindler,. Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin's lymphoma. Leuk Lymphoma. 1998;30:525–537.
39. B.Falini, A.Bolognesi, L.Flenghi,. Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin. Lancet. 1992;339:1195–1196.
40. C.F.LeMaistre, F.E.Craig, C.Meneghetti,. Phase I trial of a 90-minute infusion of the fusion toxin DAB486IL-2 in hematological cancers. Cancer Res. 1993;53:3930–3934.
41. R.J.Kreitman, W.H.Wilson, J.D.White,. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. 2000;18:1622–1636.
42. J.E.Janik, J.C.Morris, D.O'Mahony,. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma. Proc Natl Acad Sci USA. 2015;112:13045–13050.
43. A.Younes, Y.Oki, P.McLaughlin,. Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma. Blood. 2012;119:4123–4128.
44. P.Borchmann, H.Haverkamp, A.Lohri,. Addition of Rituximab to BEACOPPescalated to improve the outcome of early interim PET positive advanced stage Hodgkin lymphoma patients: second planned interim analysis of the HD18 study. Blood (Suppl). 2014;124: Abstract 500.
45. D.A.Eichenauer, M.Fuchs, A.Pluetschow,. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011;118:4363–4365.
46. H.Schulz, U.Rehwald, F.Morschhauser,. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008;111:109–111.
47. D.A.Eichenauer, H.Goergen, A.Plutschow,. Ofatumumab in relapsed nodular lymphocyte-predominant Hodgkin lymphoma: results of a phase II study from the German Hodgkin study group. Leukemia. 2015. [Epub ahead of print]. DOI: 10.1038/leu.2015.321.
48. P.Borchmann, R.Schnell, I.Fuss,. Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma. Blood. 2002;100:3101–3107.
49. F.Hartmann, C.Renner, W.Jung,. Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. Blood. 1997;89:2042–2047.
50. F.Hartmann, C.Renner, W.Jung,. Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: role of infusion schedule and costimulation with cytokines. Clin Cancer Res. 2001;7:1873–1881.
51. A.Rothe, S.Sasse, M.S.Topp,. 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.
52. X.Zhao, N.Rajasekaran, U.Reusch,. CD30/CD16A Tandab AFM13-induced target cell lysis by NK-cells is enhanced by CD137 co-stimulation and blocking PD-1. Blood (Suppl). 2015;126: Abstract 2747.
53. A.Younes, A.K.Gopal, S.E.Smith,. 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.
54. A.K.Gopal, R.Chen, S.E.Smith,. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125:1236–1243.
55. C.H.Moskowitz, A.Nademanee, T.Masszi,. 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.
56. P.Borchmann, D.A.Eichenauer, A.Pluetschow,. Targeted Beacopp variants in patients with newly diagnosed advanced stage classical Hodgkin lymphoma: Final Analysis of a Randomized Phase II Study. Blood (Suppl). 2015;126: Abstract 580.
57. A.Younes, J.M.Connors, S.I.Park,. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013;14:1348–1356.
58. M.E.Keir, M.J.Butte, G.J.Freeman,. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
59. W.Zou, L.Chen Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467–477.
60. H.T.Jin, R.Ahmed, T.Okazaki Role of PD-1 in regulating T-cell immunity. Curr Top Microbiol Immunol. 2011;350:17–37.
61. Y.Zhang, S.Huang, D.Gong,. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol. 2010;7:389–395.
62. M.G.Roemer, R.H.Advani, A.H.Ligon,. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. Blood (Suppl). 2015;126: Abstract 176.
63. J.J.Oudejans, N.M.Jiwa, J.A.Kummer,. Analysis of major histocompatibility complex class I expression on Reed-Sternberg cells in relation to the cytotoxic T-cell response in Epstein-Barr virus-positive and -negative Hodgkin's disease. Blood. 1996;87:3844–3851.
64. C.D.Carey, C.Connelly, E.Gjini,. Quantitative assessment of PD-L1 expression in classical Hodgkin lymphoma suggests a critical role for tumor associated macrophages in suppressing anti-tumor immunity. Blood (Suppl). 2015;126: Abstract 1440.
65. D.L.Barber, E.J.Wherry, D.Masopust,. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439:682–687.
66. N.A.Rizvi, J.Mazieres, D.Planchard,. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16:257–265.
67. N.A.Rizvi, M.D.Hellmann, A.Snyder,. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128.
68. C.Robert, J.Schachter, G.V.Long,. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–2532.
69. M.A.Postow, J.Chesney, A.C.Pavlick,. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–2017.
70. S.Champiat, O.Lambotte, E.Barreau,. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016;27:559–574.
71. J.Naidoo, D.B.Page, B.T.Li,. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2016;26:2375–2391.
72. S.M.Ansell, A.M.Lesokhin, I.Borrello,. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311–319.
73. S.Ansell, P.Armand, J.M.Timmerman,. Nivolumab in patients (Pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow-up of a phase 1 Study (CA209-039). Blood (Suppl). 2015;126: Abstract 583.
74. C.Herbaux, J.Gauthier, P.Brice,. Nivolumab is effective and reasonably safe in relapsed or refractory Hodgkin's lymphoma after allogeneic hematopoietic cell transplantation: a study from the Lysa and SFGM-TC. Blood (Suppl). 2015;126: Abstract 3979.
75. P.Armand, M.A.Shipp, V.Ribrag,. PD-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure: safety, efficacy, and biomarker assessment. Blood (Suppl). 2015;126: Abstract 584.
76. A.Bashey, B.Medina, S.Corringham,. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009;113:1581–1588.
77. C.S.Diefenbach, F.Hong, J.B.Cohen,. Preliminary safety and efficacy of the combination of brentuximab vedotin and ipilimumab in relapsed/refractory Hodgkin lymphoma: a trial of the ECOG-ACRIN Cancer Research Group (E4412). Blood (Suppl). 2015;126: Abstract 585.
78. C.M.Bollard, S.Gottschalk, V.Torrano,. 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.
79. C.A.Ramos, B.Ballard, E.Liu,. Chimeric T cells for therapy of CD30+ Hodgkin and non-Hodgkin lymphomas. Blood (Suppl). 2015;126: Abstract 185.
80. A.Leen, I.Tzannou, M.Bilgi,. Immunotherapy for lymphoma using T cells targeting multiple tumor associated antigens. Blood (Suppl). 2015;126: Abstract 186.
81. P.J.Bröckelmann, H.Müller, O.Casasnovas,. Risk factors and a prognostic score for progression free survival after treatment with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory hodgkin lymphoma (rrHL). Blood (Suppl). 2015;126: Abstract 1978.
82. E.B.Golden, A.Chhabra, A.Chachoua,. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol. 2015;16:795–803.
83. M.A.Postow, M.K.Callahan, C.A.Barker,. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–931.
84. L.Deng, H.Liang, B.Burnette,. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124:687–695.
85. A.Kalbasi, C.H.June, N.Haas,. Radiation and immunotherapy: a synergistic combination. J Clin Invest. 2013;123:2756–2763.
86. C.Tang, X.Wang, H.Soh,. Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res. 2014;2:831–838.
87. L.Zitvogel, L.Apetoh, F.Ghiringhelli,. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73.
88. C.Twyman-Saint Victor, A.J.Rech, A.Maity,. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–377.
89. C.Robert, G.V.Long, B.Brady,. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330.
90. T.J.Lynch, I.Bondarenko, A.Luft,. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012;30:2046–2054.
91. A.Younes, A.Sureda, D.Ben-Yehuda,. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012;30:2197–2203.
92. Y.Oki, D.Buglio, J.Zhang,. Immune regulatory effects of panobinostat in patients with Hodgkin lymphoma through modulation of serum cytokine levels and T-cell PD1 expression. Blood Cancer J. 2014;4:e236.