Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy
Abstract
:1. Introduction
2. Brentuximab Vedotin
3. Checkpoint Inhibitors
4. Everolimus
5. Histone Deacetylase Inhibitors: Panobinostat and Mocetinostat
6. Lenalidomide
7. JAK Inhibitors
8. CAR-T Cell in Relapsed/Refractory HL
9. Conclusions
Funding
Conflicts of Interest
References
- Jaffe, E.; Arber, D.A.; Campo, E.; Harris, N.L.; Quintanilla-Fend, L. Hematopathology. In Hematopathology; Elsevier: Amsterdam, The Netherlands, 2016. [Google Scholar]
- Johnson, P.; Federico, M.; Kirkwood, A.; Fosså, A.; Berkahn, L.; Carella, A.; d’Amore, F.; Enblad, G.; Franceschetto, A.; Fulham, M.; et al. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma. N. Engl. J. Med. 2016. [Google Scholar] [CrossRef] [PubMed]
- Josting, A.; Rudolph, C.; Mapara, M.; Glossmann, J.P.; Sienawski, M.; Sieber, M.; Kirchner, H.H.; Dörken, B.; Hossfeld, D.K.; Kisro, J.; et al. Cologne High-Dose Sequential Chemotherapy in Relapsed and Refractory Hodgkin Lymphoma: Results of a Large Multicenter Study of the German Hodgkin Lymphoma Study Group (GHSG). Ann. Oncol. 2005. [Google Scholar] [CrossRef]
- Moskowitz, C.H.; Nimer, S.D.; Zelenetz, A.D.; Trippett, T.; Hedrick, E.E.; Filippa, D.A.; Louie, D.; Gonzales, M.; Walits, J.; Coady-Lyons, N.; 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. [Google Scholar] [CrossRef]
- Bartlett, N.L.; Niedzwiecki, D.; Johnson, J.L.; Friedberg, J.W.; Johnson, K.B.; van Besien, K.; Zelenetz, A.D.; Cheson, B.D.; Canellos, G.P. Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin (GVD), a Salvage Regimen in Relapsed Hodgkin’s Lymphoma: CALGB 59804. Ann. Oncol. 2007. [Google Scholar] [CrossRef]
- Santoro, A.; Magagnoli, M.; Spina, M.; Pinotti, G.; Siracusano, L.; Michieli, M.; Nozza, A.; Sarina, B.; Morenghi, E.; Castagna, L.; et al. Ifosfamide, Gemcitabine, and Vinorelbine: A New Induction Regimen for Refractory and Relapsed Hodgkin’s Lymphoma. Haematologica 2007. [Google Scholar] [CrossRef]
- Kuruvilla, J.; Nagy, T.; Pintilie, M.; Tsang, R.; Keating, A.; Crump, M. Similar Response Rates and Superior Early Progression-Free Survival with Gemcitabine, Dexamethasone, and Cisplatin Salvage Therapy Compared with Carmustine, Etoposide, Cytarabine, and Melphalan Salvage Therapy Prior to Autologous Stem Cell Transplantation for Recurrent or Refractory Hodgkin Lymphoma. Cancer 2006. [Google Scholar] [CrossRef]
- Moskowitz, C.H.; Matasar, M.J.; Zelenetz, A.D.; Nimer, S.D.; Gerecitano, J.; Hamlin, P.; Horwitz, S.; Moskowitz, A.J.; Noy, A.; Palomba, L.; et al. Normalization of Pre-ASCT, FDG-PET Imaging with Second-Line, Non-Cross-Resistant, Chemotherapy Programs Improves Event-Free Survival in Patients with Hodgkin Lymphoma. Blood 2012. [Google Scholar] [CrossRef] [PubMed]
- Kuruvilla, J.; Keating, A.; Crump, M. How I Treat Relapsed and Refractory Hodgkin Lymphoma. Blood 2011. [Google Scholar] [CrossRef] [PubMed]
- Roemer, M.G.M.; Advani, R.H.; Ligon, A.H.; Natkunam, Y.; Redd, R.A.; Homer, H.; Connelly, C.F.; Sun, H.H.; Daadi, S.E.; Freeman, G.J.; et al. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J. Clin. Oncol. 2016. [Google Scholar] [CrossRef]
- Falini, B.; Pileri, S.; Pizzolo, G.; Dürkop, H.; Flenghi, L.; Stirpe, F.; Martelli, M.F.; Stein, H. CD30 (Ki-1) Molecule: A New Cytokine Receptor of the Tumor Necrosis Factor Receptor Superfamily as a Tool for Diagnosis and Immunotherapy. Blood 1995, 85, 1–4. [Google Scholar] [PubMed]
- Matsumoto, K.; Terakawa, M.; Miura, K.; Fukuda, S.; Nakajima, T.; Saito, H. Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment in Vitro. J. Immunol. 2004. [Google Scholar] [CrossRef]
- Bartlett, N.L.; Younes, A.; Carabasi, M.H.; Forero, A.; Rosenblatt, J.D.; Leonard, J.P.; Bernstein, S.H.; Bociek, R.G.; Lorenz, J.M.; Hart, B.W.; et al. A Phase 1 Multidose Study of SGN-30 Immunotherapy in Patients with Refractory or Recurrent CD30+ Hematologic Malignancies. Blood 2008. [Google Scholar] [CrossRef]
- Ansell, S.M.; Horwitz, S.M.; Engert, A.; Khan, K.D.; Lin, T.; Strair, R.; Keler, T.; Graziano, R.; Blanset, D.; Yellin, M.; et al. Phase I/II Study of an Anti-CD30 Monoclonal Antibody (MDX-060) in Hodgkin’s Lymphoma and Anaplastic Large-Cell Lymphoma. J. Clin. Oncol. 2007. [Google Scholar] [CrossRef]
- Alperovich, A.; Younes, A. Targeting CD30 Using Brentuximab Vedotin in the Treatment of Hodgkin Lymphoma. Cancer J. 2016. [Google Scholar] [CrossRef]
- Younes, A.; Gopal, A.K.; Smith, S.E.; Ansell, S.M.; Rosenblatt, J.D.; Savage, K.J.; Ramchandren, R.; Bartlett, N.L.; Cheson, B.D.; De Vos, S.; 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. [Google Scholar] [CrossRef]
- Gandhi, M.D.; Evens, A.M.; Fenske, T.S.; Hamlin, P.; Coiffier, B.; Engert, A.; Moskowitz, A.J.; Ghosh, N.; Petrich, A.M.; Lomasney, J.; et al. Pancreatitis in Patients Treated with Brentuximab Vedotin: A Previously Unrecognized Serious Adverse Event. Blood 2014. [Google Scholar] [CrossRef]
- Moskowitz, C.H.; Nademanee, A.; Masszi, T.; Agura, E.; Holowiecki, J.; Abidi, M.H.; Chen, A.I.; Stiff, P.; Gianni, A.M.; Carella, A.; 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. [Google Scholar] [CrossRef]
- Chen, R.; Palmer, J.M.; Martin, P.; Tsai, N.; Kim, Y.; Chen, B.T.; Popplewell, L.; Siddiqi, T.; Thomas, S.H.; Mott, M.; et al. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma. Biol. Blood Marrow Transplant. 2015. [Google Scholar] [CrossRef]
- Moskowitz, A.J.; Schöder, H.; Yahalom, J.; McCall, S.J.; Fox, S.Y.; Gerecitano, J.; Grewal, R.; Hamlin, P.A.; Horwitz, S.; Kobos, R.; 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. [Google Scholar] [CrossRef]
- Gandhi, V. Metabolism and Mechanisms of Action of Bendamustine: Rationales for Combination Therapies. Semin. Oncol. 2002. [Google Scholar] [CrossRef]
- Moskowitz, A.J.; Hamlin, P.A.; Perales, M.A.; Gerecitano, J.; Horwitz, S.M.; Matasar, M.J.; Noy, A.; Palomba, M.L.; Portlock, C.S.; Straus, D.J.; et al. Phase Ii Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. J. Clin. Oncol. 2013. [Google Scholar] [CrossRef] [PubMed]
- LaCasce, A.S.; Gregory Bociek, R.; Sawas, A.; Caimi, P.; Agura, E.; Matous, J.; Ansell, S.M.; Crosswell, H.E.; Islas-Ohlmayer, M.; Behler, C.; et al. Brentuximab Vedotin plus Bendamustine: A Highly Active First Salvage Regimen for Relapsed or Refractory Hodgkin Lymphoma. Blood 2018. [Google Scholar] [CrossRef] [PubMed]
- Josting, A.; Rudolph, C.; Reiser, M.; Mapara, M.; Sieber, M.; Kirchner, H.H.; Dörken, B.; Hossfeld, D.K.; Diehl, V.; Engert, A. Time-Intensified Dexamethasone/Cisplatin/Cytarabine: An Effective Salvage Therapy with Low Toxicity in Patients with Relapsed and Refractory Hodgkin’s Disease. Ann. Oncol. 2002. [Google Scholar] [CrossRef]
- Green, M.R.; Monti, S.; Rodig, S.J.; Juszczynski, P.; Currie, T.; O’Donnell, E.; Chapuy, B.; Takeyama, K.; Neuberg, D.; Golub, T.R.; 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. [Google Scholar] [CrossRef] [PubMed]
- Chen, B.J.; Chapuy, B.; Ouyang, J.; Sun, H.H.; Roemer, M.G.M.; Xu, M.L.; Yu, H.; Fletcher, C.D.M.; Freeman, G.J.; Shipp, M.A.; et al. PD-L1 Expression Is Characteristic of a Subset of Aggressive B-Cell Lymphomas and Virus-Associated Malignancies. Clin. Cancer Res. 2013. [Google Scholar] [CrossRef] [PubMed]
- Ansell, S.M.; Lesokhin, A.M.; Borrello, I.; Halwani, A.; Scott, E.C.; Gutierrez, M.; Schuster, S.J.; Millenson, M.M.; Cattry, D.; Freeman, G.J.; et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. N. Engl. J. Med. 2015. [Google Scholar] [CrossRef] [PubMed]
- Younes, A.; Santoro, A.; Shipp, M.; Zinzani, P.L.; Timmerman, J.M.; Ansell, S.; Armand, P.; Fanale, M.; Ratanatharathorn, V.; Kuruvilla, J.; 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. [Google Scholar] [CrossRef]
- Armand, P.; Engert, A.; Younes, A.; Fanale, M.; Santoro, A.; Zinzani, P.L.; Timmerman, J.M.; Collins, G.P.; Ramchandren, R.; Cohen, J.B.; 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. [Google Scholar] [CrossRef]
- Herrera, A.F.; Moskowitz, A.J.; Bartlett, N.L.; Vose, J.M.; Ramchandren, R.; Feldman, T.A.; LaCasce, A.S.; Ansell, S.M.; Moskowitz, C.H.; Fenton, K.; et al. Interim Results of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma. Blood 2018. [Google Scholar] [CrossRef]
- Armand, P.; Shipp, M.A.; Ribrag, V.; Michot, J.M.; Zinzani, P.L.; Kuruvilla, J.; Snyder, E.S.; Ricart, A.D.; Balakumaran, A.; Rose, S.; et al. Programmed Death-1 Blockade with Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure. J. Clin. Oncol. 2016. [Google Scholar] [CrossRef]
- Chen, R.; Zinzani, P.L.; Fanale, M.A.; Armand, P.; Johnson, N.A.; Brice, P.; Radford, J.; Ribrag, V.; Molin, D.; Vassilakopoulos, T.P.; et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J. Clin. Oncol. 2017. [Google Scholar] [CrossRef] [PubMed]
- Ansell, S.; Gutierrez, M.; Shipp, M.A.; Gladstone, D.; Moskowitz, A.; Borello, I.; Popa-Mckiver, M.; Farsaci, B.; Zhu, L.; Lesokhin, A.M.; et al. Phase 1 Study of Nivolumab in Combination with Ipilimumab for Relapsed or Refractory Hematologic Malignancies (CheckMate 039). Blood 2016, 128, 183. [Google Scholar]
- Dutton, A.; Reynolds, G.M.; Dawson, C.W.; Young, L.S.; Murray, P.G. 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. 2005. [Google Scholar] [CrossRef] [PubMed]
- Nagel, S.; Scherr, M.; Quentmeier, H.; Kaufmann, M.; Zaborski, M.; Drexler, H.G.; MacLeod, R.A.F. HLXB9 Activates IL6 in Hodgkin Lymphoma Cell Lines and Is Regulated by PI3K Signalling Involving E2F3. Leukemia 2005. [Google Scholar] [CrossRef] [PubMed]
- Jundt, F.; Raetzel, N.; Müller, C.; Calkhoven, C.F.; Kley, K.; Mathas, S.; Lietz, A.; Leutz, A.; Dörken, B. A Rapamycin Derivative (Everolimus) Controls Proliferation through down-Regulation of Truncated CCAAT Enhancer Binding Protein β and NF-ΒB Activity in Hodgkin and Anaplastic Large Cell Lymphomas. Blood 2005. [Google Scholar] [CrossRef]
- Johnston, P.B.; Inwards, D.J.; Colgan, J.P.; Laplant, B.R.; Kabat, B.F.; Habermann, T.M.; Micallef, I.N.; Porrata, L.F.; Ansell, S.M.; Reeder, C.B.; et al. A Phase II Trial of the Oral MTOR Inhibitor Everolimus in Relapsed Hodgkin Lymphoma. Am. J. Hematol. 2010. [Google Scholar] [CrossRef]
- Johnston, P.B.; Pinter-Brown, L.C.; Warsi, G.; White, K.; Ramchandren, R. Phase 2 Study of Everolimus for Relapsed or Refractory Classical Hodgkin Lymphoma. Exp. Hematol. Oncol. 2018. [Google Scholar] [CrossRef] [PubMed]
- Marks, P.A.; Xu, W.S. Histone Deacetylase Inhibitors: Potential in Cancer Therapy. J Cell Biochem. 2009. [Google Scholar] [CrossRef]
- Lane, A.A.; Chabner, B.A. Histone Deacetylase Inhibitors in Cancer Therapy. J. Clin. Oncol. 2009. [Google Scholar] [CrossRef] [PubMed]
- Lemoine, M.; Derenzini, E.; Buglio, D.; Medeiros, L.J.; Davis, R.E.; Zhang, J.; Ji, Y.; Younes, A. The Pan-Deacetylase Inhibitor Panobinostat Induces Cell Death and Synergizes with Everolimus in Hodgkin Lymphoma Cell Lines. Blood 2012. [Google Scholar] [CrossRef]
- Younes, A.; Sureda, A.; Ben-Yehuda, D.; Zinzani, P.L.; Ong, T.C.; Prince, H.M.; Harrison, S.J.; Kirschbaum, M.; Johnston, P.; Gallagher, J.; et al. Panobinostat in Patients with Relapsed/Refractory Hodgkin’s Lymphoma after Autologous Stem-Cell Transplantation: Results of a Phase II Study. J. Clin. Oncol. 2012. [Google Scholar] [CrossRef] [PubMed]
- Oki, Y.; Buglio, D.; Fanale, M.; Fayad, L.; Copeland, A.; Romaguera, J.; Kwak, L.W.; Pro, B.; De Castro Faria, S.; Neelapu, S.; et al. Phase i Study of Panobinostat plus Everolimus in Patients with Relapsed or Refractory Lymphoma. Clin. Cancer Res. 2013. [Google Scholar] [CrossRef] [PubMed]
- Hu, B.; Younes, A.; Westin, J.R.; Turturro, F.; Claret, L.; Feng, L.; Fowler, N.; Neelapu, S.; Romaguera, J.; Hagemeister, F.B.; et al. Phase-I and Randomized Phase-II Trial of Panobinostat in Combination with ICE (Ifosfamide, Carboplatin, Etoposide) in Relapsed or Refractory Classical Hodgkin Lymphoma. Leuk. Lymphoma 2018. [Google Scholar] [CrossRef] [PubMed]
- Younes, A.; Oki, Y.; Bociek, R.G.; Kuruvilla, J.; Fanale, M.; Neelapu, S.; Copeland, A.; Buglio, D.; Galal, A.; Besterman, J.; et al. Mocetinostat for Relapsed Classical Hodgkin’s Lymphoma: An Open-Label, Single-Arm, Phase 2 Trial. Lancet Oncol. 2011. [Google Scholar] [CrossRef]
- Fehniger, T.A.; Larson, S.; Trinkaus, K.; Siegel, M.J.; Cashen, A.F.; Blum, K.A.; Fenske, T.S.; Hurd, D.D.; Goy, A.; Schneider, S.E.; et al. A Phase 2 Multicenter Study of Lenalidomide in Relapsed or Refractory Classical Hodgkin Lymphoma. Blood 2011. [Google Scholar] [CrossRef] [PubMed]
- Chanan-Khan, A.A.; Cheson, B.D. Lenalidomide for the Treatment of B-Cell Malignancies. J. Clin. Oncol. 2008. [Google Scholar] [CrossRef]
- Maly, J.J.; Christian, B.A.; Zhu, X.; Wei, L.; Sexton, J.L.; Jaglowski, S.M.; Devine, S.M.; Fehniger, T.A.; Wagner-Johnston, N.D.; Phelps, M.A.; et al. A Phase I/II Trial of Panobinostat in Combination With Lenalidomide in Patients With Relapsed or Refractory Hodgkin Lymphoma. Clin. Lymphoma Myeloma Leuk. 2017. [Google Scholar] [CrossRef]
- Younes, A.; Romaguera, J.; Fanale, M.; McLaughlin, P.; Hagemeister, F.; Copeland, A.; Neelapu, S.; Kwak, L.; Shah, J.; De Castro Faria, S.; et al. Phase I Study of a Novel Oral Janus Kinase 2 Inhibitor, SB1518, in Patients with Relapsed Lymphoma: Evidence of Clinical and Biologic Activity in Multiple Lymphoma Subtypes. J. Clin. Oncol. 2012. [Google Scholar] [CrossRef]
- Van Den Neste, E.; André, M.; Gastinne, T.; Stamatoullas, A.; Haioun, C.; Belhabri, A.; Reman, O.; Casasnovas, O.; Ghesquieres, H.; Verhoef, G.; et al. A Phase II Study of the Oral JAK1/JAK2 Inhibitor Ruxolitinib in Advanced Relapsed/Refractory Hodgkin Lymphoma. Haematologica 2018. [Google Scholar] [CrossRef]
- Phillips, T.J.; Forero-Torres, A.; Sher, T.; Diefenbach, C.S.; Johnston, P.; Talpaz, M.; Pulini, J.; Zhou, L.; Scherle, P.; Chen, X.; et al. Phase 1 Study of the PI3Kd Inhibitor INCB040093 6 JAK1 Inhibitor Itacitinib in Relapsed/Refractory B-Cell Lymphoma. Blood 2018. [Google Scholar] [CrossRef]
- Kochenderfer, J.N.; Dudley, M.E.; Kassim, S.H.; Somerville, R.P.T.; Carpenter, R.O.; Maryalice, S.S.; Yang, J.C.; Phan, G.Q.; Hughes, M.S.; Sherry, R.M.; et al. Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated with Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor. J. Clin. Oncol. 2015. [Google Scholar] [CrossRef] [PubMed]
- Brentjens, R.J.; Davila, M.L.; Riviere, I.; Park, J.; Wang, X.; Cowell, L.G.; Bartido, S.; Stefanski, J.; Taylor, C.; Olszewska, M.; et al. CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia. Sci. Transl. Med. 2013. [Google Scholar] [CrossRef] [PubMed]
- Turtle, C.J.; Hanafi, L.A.; Berger, C.; Hudecek, M.; Pender, B.; Robinson, E.; Hawkins, R.; Chaney, C.; Cherian, S.; Chen, X.; 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. [Google Scholar] [CrossRef] [PubMed]
- Ramos, C.A.; Ballard, B.; Zhang, H.; Dakhova, O.; Gee, A.P.; Mei, Z.; Bilgi, M.; Wu, M.F.; Liu, H.; Grilley, B.; et al. Clinical and Immunological Responses after CD30-Specific Chimeric Antigen Receptor-Redirected Lymphocytes. J. Clin. Invest. 2017. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.M.; Wu, Z.Q.; Wang, Y.; Guo, Y.L.; Dai, H.R.; Wang, X.H.; Li, X.; Zhang, Y.J.; Zhang, W.Y.; Chen, M.X.; et al. Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase i Trial. Clin. Cancer Res. 2017. [Google Scholar] [CrossRef]
- Grover, N.S.; Park, S.I.; Ivanova, A.; Eldridge, P.; McKay, K.; Cheng, C.J.; Laing, S.; Covington, D.; West, J.; Sharf, S.E.; et al. Clinical Responses to CAR.CD30-T Cells in Patients with CD30+ Lymphomas Relapsed after Multiple Treatments Including Brentuximab Vedotin. Blood 2018. [Google Scholar] [CrossRef]
- Bollard, C.M.; Tripic, T.; Cruz, C.R.; Dotti, G.; Gottschalk, S.; Torrano, V.; Dakhova, O.; Carrum, G.; Ramos, C.A.; Liu, H.; et al. Tumor-Specific t-Cells Engineered to Overcome Tumor Immune Evasion Induce Clinical Responses in Patients with Relapsed Hodgkin Lymphoma. J. Clin. Oncol. 2018. [Google Scholar] [CrossRef] [PubMed]
- Younes, A.; Bartlett, N.L.; Leonard, J.P.; Kennedy, D.A.; Lynch, C.M.; Sievers, E.L.; Forero-Torres, A. Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas. N. Engl. J. Med. 2010. [Google Scholar] [CrossRef] [PubMed]
- Gopal, A.K.; Fanale, M.A.; Moskowitz, C.H.; Shustov, A.R.; Mitra, S.; Ye, W.; Younes, A.; Moskowitz, A.J. Phase II Study of Idelalisib, a Selective Inhibitor of PI3Kδ, for Relapsed/Refractory Classical Hodgkin Lymphoma. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2017. [Google Scholar] [CrossRef] [PubMed]
Agents | Author | Year of Publication | Study Charateristics | N | Results |
---|---|---|---|---|---|
BV | Younes et al. [59] | 2010 | Phase I | 45 | Tumor Regression in 36/42 patient |
BV | Younes et al. [16] | 2012 | Phase II | 102 | ORR 75% CR 34% |
BV + augICE | Moskowitz et al. [20] | 2015 | Phase II | 46 | PET neg status in 76%- |
BV | Chen et al. [19] | 2015 | Phase II | 37 | ORR 68% CR 35% |
BV + Bendamustine | LaCasce et al. [23] | 2018 | Phase I/II | 55 | ORR 92.5% CR 73.6% |
Nivolumab | Ansell et al. [27] | 2015 | Phase I | 23 | ORR 87% CR 17% |
Nivolumab | Younes et al. [28] | 2016 | Phase II | 80 | ORR 66.3% CR 9% |
Nivolumab (Checkmate 205 Trial) | Armand et al. [29] | 2018 | Phase II | 243 | ORR 69% CR 16% |
BV + Nivolumab | Herrera et al. [30] | 2018 | Phase I/II | 62 | ORR 82% CR 61% |
Pembrolizumab | Armand et al. [31] | 2016 | Phase Ib | 31 | ORR 65% CR 16% |
Pembrolizumab | Chen et al. [32] | 2017 | Phase II | 210 | ORR 69% CR 22.4% |
Everolimus | Johnston et al. [38] | 2018 | Phase II | 57 | ORR 45.6% CR 8.8% |
Panobinostat | Younes et al. [42] | 2012 | Phase II | 129 | ORR 27% CR 4% |
Everolimus + Panobinostat | Oki et al. [43] | 2013 | Phase I | 30 | ORR 43% CR 15% |
Lenalidomide | Fehniger et al. [46] | 2011 | Phase II | 38 | ORR 19% CR 2.7% |
Lenalidomide + Panobinostat | Maly et al. [48] | 2017 | Phase I/II | 24 | ORR 16.7% CR 8.3% |
Mocetinostat | Younes et al. [45] | 2011 | Phase II | 51 | Disease Control 29.4% |
Idelalisib | Gopal et al. [60] | 2017 | Phase II | 25 | ORR 25% CR 4% |
Ruxolitinib | Van DenNaste [50] | 2018 | Phase II | 33 | ORR 9.4%, CR 0% |
PI3K-inhib + JAK1 inhibitor | Phillips [51] | 2018 | Phase I | 39 | ORR 67% |
CAR-T Cell | Ramos [55] | 2017 | Phase I | 7 | 2 CR, 3 stable disease |
CAR-T Cell | Wang [56] | 2017 | Phase I | 17 | 7 PR, 6 stable disease |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mina, A.A.; Vakkalagadda, C.; Pro, B. Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy. Cancers 2019, 11, 421. https://doi.org/10.3390/cancers11030421
Mina AA, Vakkalagadda C, Pro B. Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy. Cancers. 2019; 11(3):421. https://doi.org/10.3390/cancers11030421
Chicago/Turabian StyleMina, Alain Antoine, Chetan Vakkalagadda, and Barbara Pro. 2019. "Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy" Cancers 11, no. 3: 421. https://doi.org/10.3390/cancers11030421