Abstract
Brentuximab vedotin (BV) and the PD-1 inhibitors have dramatically expanded options and improved outcomes for patients with relapsed or refractory Hodgkin lymphoma (HL). For patients with disease progression following BV, PD-1 inhibitors, and autologous stem cell transplant (ASCT), treatment options are limited. Additional classes of drugs have been found to be effective for HL, including drugs that target the PI3-kinase (PI3K) pathway, histone deacetylase (HDAC) inhibitors, as well as immune modulatory agents. These agents target both the Hodgkin Reed-Sternberg cells as well as the tumor microenvironment. While these targeted drugs are options for patients who have progressed after BV or PD-1 inhibitors, there is good rationale for combining some of these agents with either BV or PD-1 inhibitors to improve response rates or durability. Such combinations are under investigation in clinical trials. Emerging therapies for HL include the anti-CD25 antibody drug conjugate, camidanlumab, as well as other therapies that target CD30 such as anti-CD30 chimeric antigen receptor (CAR)-T cells and the bispecific antibody, AFM-13. Newer targeted agents, emerging therapies, as well as studies evaluating novel combinations will be reviewed.
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References
Dutton A, Reynolds GM, Dawson CW, Young LS, Murray PG (2005) Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin’s lymphoma cells through a mechanism involving Akt kinase and mTOR. J Pathol 205:498–506
Georgakis GV, Li Y, Rassidakis GZ, Medeiros LJ, Mills GB, Younes A (2006) Inhibition of the phosphatidylinositol-3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma. Br J Haematol 132:503–511
Johnston PB, Pinter-Brown LC, Warsi G, White K, Ramchandren R (2018) Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma. Exp Hematol Oncol 7:12
Meadows SA, Vega F, Kashishian A et al (2012) PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood 119:1897–1900
Gopal AK, Fanale MA, Moskowitz CH et al (2017) Phase II study of idelalisib, a selective inhibitor of PI3Kdelta, for relapsed/refractory classical Hodgkin lymphoma. Ann Oncol 28:1057–1063
Lemoine M, Derenzini E, Buglio D et al (2012) The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with everolimus in Hodgkin lymphoma cell lines. Blood 119:4017–4025
Oki Y, Buglio D, Fanale M et al (2013) Phase I study of Panobinostat plus Everolimus in patients with relapsed or refractory lymphoma. Clin Cancer Res 19:6882–6890
Ali K, Soond DR, Pineiro R et al (2014) Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 510:407–411
Marshall NA, Galvin KC, Corcoran AM, Boon L, Higgs R, Mills KH (2012) Immunotherapy with PI3K inhibitor and toll-like receptor agonist induces IFN-gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Res 72:581–591
Buglio D, Georgakis GV, Hanabuchi S et al (2008) Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines. Blood 112:1424–1433
Buglio D, Khaskhely NM, Voo KS, Martinez-Valdez H, Liu YJ, Younes A (2011) HDAC11 plays an essential role in regulating OX40 ligand expression in Hodgkin lymphoma. Blood 117:2910–2917
Kirschbaum MH, Goldman BH, Zain JM et al (2007) Vorinostat (Suberoylanilide Hydroxamic acid) in relapsed or refractory Hodgkin lymphoma: SWOG 0517. ASH Annual Meeting Abstracts 110:2574
Younes A, Sureda A, Ben-Yehuda D et al (2012) Panobinostat in patients with relapsed/refractory Hodgkin’s lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol Off J Am Soc Clin Oncol 30:2197–2203
Younes A, Oki Y, Bociek RG et al (2011) Mocetinostat for relapsed classical Hodgkin’s lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol 12:1222–1228
Batlevi CL, Kasamon Y, Bociek RG et al (2016) ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. Haematologica 101:968–975
Skov S, Pedersen MT, Andresen L, Straten PT, Woetmann A, Odum N (2005) Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase Kinase-3–dependent expression of MHC class I–related chain a and B. Cancer Res 65:11136–11145
Kotla V, Goel S, Nischal S et al (2009) Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol 2:36
Gribben JG, Fowler N, Morschhauser F (2015) Mechanisms of action of Lenalidomide in B-cell non-Hodgkin lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 33:2803–2811
Boll B, Borchmann P, Topp MS et al (2010) Lenalidomide in patients with refractory or multiple relapsed Hodgkin lymphoma. Br J Haematol 148:480–482
Fehniger TA, Larson S, Trinkaus K et al (2011) A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood 118:5119–5125
Maly JJ, Christian BA, Zhu X et al (2017) A phase I/II trial of Panobinostat in combination with Lenalidomide in patients with relapsed or refractory Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 17:347–353
Padrnos L, Ernst B, Dueck AC et al (2018) A novel combination of the mTORC1 inhibitor everolimus and the immunomodulatory drug lenalidomide produces durable responses in patients with heavily pretreated relapsed lymphoma. Clin Lymphoma Myeloma Leuk 18:664–672.e2
Ramos CA, Ballard B, Zhang H et al (2017) Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest 127:3462–3471
Ramos CA, Rouce R, Robertson CS et al (2018) In vivo fate and activity of second- versus third-generation CD19-specific CAR-T cells in B cell non-Hodgkin’s lymphomas. Mol Ther 26:2727–2737
Ramos CA, Bilgi M, Gerken CP et al (2018) CD30-chimeric antigen receptor (CAR) T cells for therapy of Hodgkin lymphoma (HL). Blood 132:680
Grover NS, Park SI, Ivanova A et al (2018) Clinical responses to CAR.CD30-T cells in patients with CD30+ lymphomas relapsed after multiple treatments including Brentuximab Vedotin. Blood 132:681
Rothe A, Sasse S, Topp MS et al (2015) A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood 125:4024–4031
Bartlett NL, Chen RW, Domingo-Domenech E et al (2018) A phase 1b study investigating the combination of the tetravalent bispecific NK cell engager AFM13 and Pembrolizumab in patients with relapsed/refractory Hodgkin lymphoma after Brentuximab Vedotin failure: updated safety and efficacy data. Blood 132:1620
Hamadani M, Collins GP, Samaniego F et al (2018) Phase 1 study of Adct-301 (Camidanlumab Tesirine), a novel Pyrrolobenzodiazepine-based antibody drug conjugate, in relapsed/refractory classical Hodgkin lymphoma. Blood 132:928
Spina V, Bruscaggin A, Cuccaro A et al (2018) Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma. Blood 131:2413–2425
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Moskowitz, A.J., Younes, A. (2020). Other New Agents for Hodgkin Lymphoma. In: Engert, A., Younes, A. (eds) Hodgkin Lymphoma. Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-32482-7_24
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DOI: https://doi.org/10.1007/978-3-030-32482-7_24
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