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Role of CD30 Targeting in Malignant Lymphoma

  • Lymphoma (A Engert, Section Editor)
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Opinion statement

CD30 is an important therapeutic target for the treatment of malignant lymphomas. CD30 is a member of the TNF cell receptor superfamily and is highly expressed in a variety of lymphoma subsets, including Hodgkin lymphoma and anaplastic large cell lymphoma. Initial studies evaluated the safety and efficacy of several monoclonal antibodies targeting CD30, with limited success. More recently, the anti-CD30 drug-conjugate brentuximab vedotin produced high response rates with an excellent safety profile. These results lead to the approval of brentuximab vedotin for the treatment of patients with relapsed Hodgkin lymphoma and anaplastic large cell lymphoma. Current studies are focusing on incorporating brentuximab vedotin in front-line regimens and expanding its potential clinical utility in other CD30-expressing malignancies.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Stein H, Mason DY, Gerdes J, O’Connor N, Wainscoat J, Pallesen G, et al. The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66(4):848–58.

    CAS  PubMed  Google Scholar 

  2. Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells. Nature. 1982;299(5878):65–7.

    Article  CAS  PubMed  Google Scholar 

  3. Hecht TT, Longo DL, Cossman J, Bolen JB, Hsu SM, Israel M, et al. Production and characterization of a monoclonal antibody that binds Reed-Sternberg cells. J Immunol. 1985;134(6):4231–6.

    CAS  PubMed  Google Scholar 

  4. Schwarting R, Gerdes J, Durkop H, Falini B, Pileri S, Stein H. BER-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood. 1989;74(5):1678–89.

    CAS  PubMed  Google Scholar 

  5. Durkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin’s disease. Cell. 1992;68(3):421–7.

    Article  CAS  PubMed  Google Scholar 

  6. Fonatsch C, Latza U, Durkop H, Rieder H, Stein H. Assignment of the human CD30 (Ki-1) gene to 1p36. Genomics. 1992;14(3):825–6.

    Article  CAS  PubMed  Google Scholar 

  7. Duckett CS, Gedrich RW, Gilfillan MC, Thompson CB. Induction of nuclear factor kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol. 1997;17(3):1535–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Duckett CS, Thompson CB. CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival. Genes Dev. 1997;11(21):2810–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Mir SS, Richter BW, Duckett CS. Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells. Blood. 2000;96(13):4307–12.

    CAS  PubMed  Google Scholar 

  10. Smith CA, Gruss HJ, Davis T, Anderson D, Farrah T, Baker E, et al. CD30 antigen, a marker for Hodgkin’s lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF. Cell. 1993;73(7):1349–60.

    Article  CAS  PubMed  Google Scholar 

  11. Younes A, Consoli U, Zhao S, Snell V, Thomas E, Gruss HJ, et al. CD30 ligand is expressed on resting normal and malignant human B lymphocytes. Br J Haematol. 1996;93(3):569–71.

    Article  CAS  PubMed  Google Scholar 

  12. Gruss HJ, Boiani N, Williams DE, Armitage RJ, Smith CA, Goodwin RG. Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. Blood. 1994;83(8):2045–56.

    CAS  PubMed  Google Scholar 

  13. Bowen MA, Lee RK, Miragliotta G, Nam SY, Podack ER. Structure and expression of murine CD30 and its role in cytokine production. J Immunol. 1996;156(2):442–9.

    CAS  PubMed  Google Scholar 

  14. Amakawa R, Hakem A, Kundig TM, Matsuyama T, Simard JJ, Timms E, et al. Impaired negative selection of T cells in Hodgkin’s disease antigen CD30-deficient mice. Cell. 1996;84(4):551–62.

    Article  CAS  PubMed  Google Scholar 

  15. DeYoung AL, Duramad O, Winoto A. The TNF receptor family member CD30 is not essential for negative selection. J Immunol. 2000;165(11):6170–3.

    Article  CAS  PubMed  Google Scholar 

  16. Kurts C, Carbone FR, Krummel MF, Koch KM, Miller JF, Heath WR. Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T cells. Nature. 1999;398(6725):341–4. doi:10.1038/18692.

    Article  CAS  PubMed  Google Scholar 

  17. Gaspal FM, Kim MY, McConnell FM, Raykundalia C, Bekiaris V, Lane PJ. Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory. J Immunol. 2005;174(7):3891–6.

    Article  CAS  PubMed  Google Scholar 

  18. Gerli R, Lunardi C, Vinante F, Bistoni O, Pizzolo G, Pitzalis C. Role of CD30+ T cells in rheumatoid arthritis: a counter-regulatory paradigm for Th1-driven diseases. Trends Immunol. 2001;22(2):72–7.

    Article  CAS  PubMed  Google Scholar 

  19. Sun X, Somada S, Shibata K, Muta H, Yamada H, Yoshihara H, et al. A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice. Gastroenterology. 2008;134(2):447–58. doi:10.1053/j.gastro.2007.11.004.

    Article  CAS  PubMed  Google Scholar 

  20. Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, et al. CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. J Immunol. 2010;185(12):7671–80. doi:10.4049/jimmunol.1002229.

    Article  CAS  PubMed  Google Scholar 

  21. Blazar BR, Levy RB, Mak TW, Panoskaltsis-Mortari A, Muta H, Jones M, et al. CD30/CD30 ligand (CD153) interaction regulates CD4+ T cell-mediated graft-versus-host disease. J Immunol. 2004;173(5):2933–41.

    Article  CAS  PubMed  Google Scholar 

  22. Dai Z, Li Q, Wang Y, Gao G, Diggs LS, Tellides G, et al. CD4+ CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism. J Clin Invest. 2004;113(2):310–7. doi:10.1172/JCI19727.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Younes A, Carbone A. CD30/CD30 ligand and CD40/CD40 ligand in malignant lymphoid disorders. Int J Biol Markers. 1999;14(3):135–43.

    CAS  PubMed  Google Scholar 

  24. Durkop H, Foss HD, Eitelbach F, Anagnostopoulos I, Latza U, Pileri S, et al. Expression of the CD30 antigen in non-lymphoid tissues and cells. J Pathol. 2000;190(5):613–8. doi:10.1002/(SICI)1096-9896(200004)190:5<613::AID-PATH559>3.0.CO;2-0.

    Article  CAS  PubMed  Google Scholar 

  25. Younes A, Kadin ME. Emerging applications of the tumor necrosis factor family of ligands and receptors in cancer therapy. J Clin Oncol. 2003;21(18):3526–34. doi:10.1200/JCO.2003.09.037.

    Article  CAS  PubMed  Google Scholar 

  26. de Leval L, Gaulard P. CD30+ lymphoproliferative disorders. Haematologica. 2010;95(10):1627–30. doi:10.3324/haematol.2010.029256.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Hu S, Xu-Monette ZY, Balasubramanyam A, Manyam GC, Visco C, Tzankov A, et al. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood. 2013;121(14):2715–24. doi:10.1182/blood-2012-10-461848.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Collie AMG HB, Manilich EA, et al. CD30 Immunohistochemical expression in diffuse large B-cell lymphoma is associated with decreased overall survival and the non-germinal center molecular subtype. Blood (ASH Annual Meeting Abstracts) 2013; 122 (21).

  29. Slack G SC, Sehn LH, Gascoyne RD. CD30 Expression in diffuse large B-cell lymphoma. Blood (ASH Annual Meeting Abstracts) 2012; 120 (Abstract 1558).

  30. Malamut G VV, Derrieux C, et al. Enteropathy-associated T-cell lymphoma type I, but not refractory celiac disease, strongly expresses CD30 and might benefit from brentuximab vedotin. Blood (ASH Annual Meeting Abstracts) 2013; 122 (21).

  31. Lunning MA CA, Feldstein JT, et al. CD30 Is a potential therapeutic target in patients with HTLV-1 associated adult T-cell leukemia/lymphoma presenting outside of Japan. Blood (ASH Annual Meeting Abstracts) 2012; 120.

  32. Bhatt S, Ashlock BM, Natkunam Y, Sujoy V, Chapman JR, Ramos JC, et al. CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma. Blood. 2013;122(7):1233–42. doi:10.1182/blood-2013-01-481713.

    Article  CAS  PubMed  Google Scholar 

  33. Cerny-Reiterer S SK, Juliana S, et al. Identification of the Ki-1 antigen (CD30) as a novel marker and potential therapeutic target in neoplastic mast cells in advanced systemic mastocytosis. Blood (ASH Annual Meeting Abstracts) 2013; 122 (21).

  34. Falini B, Flenghi L, Fedeli L, Broe MK, Bonino C, Stein H, et al. In vivo targeting of Hodgkin and Reed-Sternberg cells of Hodgkin’s disease with monoclonal antibody Ber-H2 (CD30): immunohistological evidence. Br J Haematol. 1992;82(1):38–45.

    Article  CAS  PubMed  Google Scholar 

  35. Falini B, Bolognesi A, Flenghi L, Tazzari PL, Broe MK, Stein H, et al. Response of refractory Hodgkin’s disease to monoclonal anti-CD30 immunotoxin. Lancet. 1992;339(8803):1195–6.

    Article  CAS  PubMed  Google Scholar 

  36. Bartlett NL, Younes A, Carabasi MH, Forero A, Rosenblatt JD, Leonard JP, et al. A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood. 2008;111(4):1848–54. doi:10.1182/blood-2007-07-099317.

    Article  CAS  PubMed  Google Scholar 

  37. Ansell SM, Horwitz SM, Engert A, Khan KD, Lin T, Strair R, 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;25(19):2764–9. doi:10.1200/JCO.2006.07.8972.

    Article  CAS  PubMed  Google Scholar 

  38. Forero-Torres A, Leonard JP, Younes A, Rosenblatt JD, Brice P, Bartlett NL, et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol. 2009;146(2):171–9. doi:10.1111/j.1365-2141.2009.07740.x.

    Article  CAS  PubMed  Google Scholar 

  39. Duvic M, Reddy SA, Pinter-Brown L, Korman NJ, Zic J, Kennedy DA, et al. A phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clin Cancer Res. 2009;15(19):6217–24. doi:10.1158/1078-0432.CCR-09-0162.

    Article  CAS  PubMed  Google Scholar 

  40. Cerveny CG, Law CL, McCormick RS, Lenox JS, Hamblett KJ, Westendorf LE, et al. Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin’s disease cells to conventional chemotherapeutics. Leukemia. 2005;19(9):1648–55. doi:10.1038/sj.leu.2403884.

    Article  CAS  PubMed  Google Scholar 

  41. Blum KA, Jung SH, Johnson JL, Lin TS, Hsi ED, Lucas DM, et al. Serious pulmonary toxicity in patients with Hodgkin’s lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcgammaRIIIa-158 V/F polymorphism. Ann Oncol. 2010;21(11):2246–54. doi:10.1093/annonc/mdq211.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Lawrence CEHP, Zalevsky J, et al. XmAbTM2513, an Fc engineered humanized anti-CD30 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating hematologic malignancies. Blood (ASH Annual Meeting Abstracts). 2007;110:2340.

    Google Scholar 

  43. Blum KA SM, Fung H, et al. Phase I study of an anti-CD30 Fc engineered humanized monoclonal antibody in Hodgkin lymphoma (HL) or anaplastic large cell lymphoma (ALCL) patients: safety, pharmacokinetics (PK), immunogenicity, and efficacy. ASCO Annu Meet (Abstracts). 2009;27:8531.

    Google Scholar 

  44. Zhukovsky ERA, von Tesckow B, et al. A Phase I study of an anti-CD30 x anti-CD16A bispecific tandab antibody, AFM13, in patients with relapsed or refractory Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts). 2013;122:5116.

    Google Scholar 

  45. Schnell R, Dietlein M, Staak JO, Borchmann P, Schomaecker K, Fischer T, et al. Treatment of refractory Hodgkin’s lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol. 2005;23(21):4669–78. doi:10.1200/JCO.2005.09.098.

    Article  CAS  PubMed  Google Scholar 

  46. Oki Y, Younes A. Brentuximab vedotin in systemic T-cell lymphoma. Expert Opin Biol Ther. 2012;12(5):623–32. doi:10.1517/14712598.2012.670216.

    Article  CAS  PubMed  Google Scholar 

  47. Katz J, Janik JE, Younes A. Brentuximab Vedotin (SGN-35). Clin Cancer Res. 2011;17(20):6428–36. doi:10.1158/1078-0432.CCR-11-0488.

    Article  CAS  PubMed  Google Scholar 

  48. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102(4):1458–65. doi:10.1182/blood-2003-01-0039.

    Article  CAS  PubMed  Google Scholar 

  49. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363(19):1812–21. doi:10.1056/NEJMoa1002965. This article describes the safety and initial clinical activity of brentuximab vedotin in patients with CD30+ lymphomas.

    Article  CAS  PubMed  Google Scholar 

  50. Fanale MA, Forero-Torres A, Rosenblatt JD, Advani RH, Franklin AR, Kennedy DA, et al. A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin Cancer Res. 2012;18(1):248–55. doi:10.1158/1078-0432.CCR-11-1425.

    Article  CAS  PubMed  Google Scholar 

  51. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, 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(18):2183–9. doi:10.1200/JCO.2011.38.0410.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6. doi:10.1200/JCO.2011.38.0402.

    Article  CAS  PubMed  Google Scholar 

  53. von Geldern G, Pardo CA, Calabresi PA, Newsome SD. PML-IRIS in a patient treated with brentuximab. Neurology. 2012;79(20):2075–7. doi:10.1212/WNL.0b013e3182749f17.

    Article  Google Scholar 

  54. Younes A, Connors JM, Park SI, Fanale M, O’Meara MM, Hunder NN, et al. 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(13):1348–56. doi:10.1016/S1470-2045(13)70501-1.

    Article  CAS  PubMed  Google Scholar 

  55. Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, et al. Brentuximab Vedotin in patients aged 60 years or older with relapsed or refractory CD30+ lymphomas: a Retrospective Evaluation of Safety and Efficacy. Leuk Lymph. 2013. doi:10.3109/10428194.2013.876496.

    Google Scholar 

  56. Evens AM HP, Advani RH, et al. Sequential brentuximab vedotin (BV) and adriamycin, vinblastine, and dacarbazine (AVD) for older patients with untreated hodgkin lymphoma (HL): preliminary toxicity findings from a phase II window study. Haematologica (9th International Symposium on Hodgkin Lymphoma Abstracts). 2013;98(supplement no. 2):26.

    Google Scholar 

  57. Abramson JS HE, Joyce R, et al. Brentuximab vedotin plus AVD as initial therapy of non-bulky limited stage classical Hodgkin lymphoma: interim analysis of an ongoing phase II trial. Haematologica (9th International Symposium on Hodgkin Lymphoma Abstracts) 2013; 90 supplement no. 2.

  58. Gopal AK CR, Smith SE, et al. Three-year follow-up data and characterization of long-term remissions from an ongoing phase 2 study of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts). 2013;122(21):4382.

    Google Scholar 

  59. Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, et al. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012;120(3):560–8. doi:10.1182/blood-2011-12-397893.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Jacobsen ED AR, Oki Y, et al. A Phase 2 study of brentuximab Vedotin in patients with relapsed or refractory CD30-positive non-Hodgkin lymphomas: interim results. Blood (ASH Annual Meeting Abstracts) 2012; 120.

  61. Bartlett NL SJ, Oki Y, et al. A Phase 2 study of brentuximab Vedotin in patients with relapsed or refractory CD30-positive non-Hodgkin lymphomas: interim results in patients with DLBCL and other B-cell lymphomas. Blood (ASH Annual Meeting Abstracts) 2013; 122 (21).

  62. Duvic M TM, Clos AL, et al. Phase II trial of brentuximab Vedotin for CD30+ cutaneous T-cell lymphomas and lymphoproliferative disorders. Blood (ASH Annual Meeting Abstracts) 2013; 122 (21).

  63. Moskowitz AJ SH, Gerecitano J, et al. PET adapted sequential salvage therapy with brentuximab vedotin and augmented ICE for trasnplant eligible patient with relapsed and refractory Hodgkin lymphoma. Haematologica (9th International Symposium on Hodgkin Lymphoma Abstracts) 2013; 98 (2).

  64. Deutsch YE, Tadmor T, Podack ER, Rosenblatt JD. CD30: an important new target in hematologic malignancies. Leuk Lymph. 2011;52(9):1641–54. doi:10.3109/10428194.2011.574761.

    Article  CAS  Google Scholar 

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Conflict of Interest

Anas Younes: Consulted for and received honorarium from Seattle Genetics and Millennium.

Anita Kumar: No potential conflicts of interest relevant to this article were reported.

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Kumar, A., Younes, A. Role of CD30 Targeting in Malignant Lymphoma. Curr. Treat. Options in Oncol. 15, 210–225 (2014). https://doi.org/10.1007/s11864-014-0275-7

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