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Anti-CD30 Antibodies for Hodgkin Lymphoma

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Abstract

Treatment of refractory or relapsed classical Hodgkin lymphoma (HL) remains challenging, but targeted immunotherapy has recently emerged as a potential treatment option for these patients. Although first-generation monoclonal anti-CD30 antibodies proved disappointing, current efforts to modify anti-CD30 antibodies to improve binding of effector cells and enhance activity appears more promising, as does the development of novel antibody-drug conjugates (ADCs). ADCs offer the potential to deliver potent therapies with minimal toxicity. One highly active ADC, brentuximab vedotin (SGN-35), combines an anti-CD30 monoclonal antibody and the antitubulin agent monomethyl auristatin E. Initial phase 1 studies of brentuximab vedotin showed a 52% overall response rate in relapsed HL, with minimal toxicity. This article highlights the development of anti-CD30 antibodies and ADCs for relapsed or refractory classical HL.

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References

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

  1. Horner MJ, Ries LAG, Krapcho M, et al. (eds): SEER Cancer Statistics Review, 1975–2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site, 2009.

  2. Jones RJ, Gocke CD, Kasamon YL, et al.: Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood 2009, 113:5920–5926.

    Article  CAS  PubMed  Google Scholar 

  3. Younes A, Romaguera J, Hagemeister F, et al.: A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer 2003, 98:310–314.

    Article  CAS  PubMed  Google Scholar 

  4. Copeland AR, Cao Y, Fanale M, et al.: Final report of a phase-II study of rituximab plus ABVD for patients with newly diagnosed advanced stage classical Hodgkin lymphoma: results of long follow up and comparison to institutional historical data [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:Abstract 1680.

  5. Phase II R-ABVD versus ABVD for advanced stage classical Hodgkin lymphoma. ClinicalTrials.gov identifier: NCT00654732. Available at http://clinicaltrials.gov/. Accessed April 2010.

  6. Jacene HA, Kasamon YL, Ambinder RF, et al.: Phase I/II dose-escalation study of tositumomab and iodine I 131 tositumomab for relapsed/refractory classical or lymphocyte-predominant Hodgkin’s lymphoma: feasibility and initial safety [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:Abstract 3059.

  7. Chetaille B, Bertucci F, Finetti P, et al.: Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome. Blood 2009, 113:2765–2675.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. LeMaistre CF, Saleh MN, Kuzel TM, et al.: Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 1998, 91:399–405.

    CAS  PubMed  Google Scholar 

  10. Clodi K, Asgari Z, Younes M, et al.: Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodkgin disease: potential therapeutic significance. Cancer 2002, 94:1–5.

    Article  CAS  PubMed  Google Scholar 

  11. Law CL, Gordon KA, Collier J, et al.: Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40. Cancer Res 2005, 65:8331–8338.

    Article  CAS  PubMed  Google Scholar 

  12. Study of HCD122 in adults with non-Hodgkin’s or Hodgkin’s lymphoma who have progressed after at least two prior therapies. ClinicalTrials.gov identifier: NCT00670592. Available at http://clinicaltrials.gov/. Accessed April 2010.

  13. Hsu PL, Hsu SM: Autocrine growth regulation of CD30 ligand in CD30-expressing Reed-Sternberg cells: distinction between Hodgkin’s disease and anaplastic large cell lymphoma. Lab Invest 2000, 80:1111–1119.

    CAS  PubMed  Google Scholar 

  14. Cerveny CG, Law CL, McCormick RS, et al.: Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin’s disease cells to conventional chemotherapy. Leukemia 2005, 19:1648–1655.

    Article  CAS  PubMed  Google Scholar 

  15. Borchmann P, Treml JF, Hansen H, et al.: The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma. Blood 2003, 102:3737–3742.

    Article  CAS  PubMed  Google Scholar 

  16. Horn-Lohrens O, Tiemann M, Lange H, et al.: Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L549 is strongly inhibited by a new CD30-specific antibody (Ki-4). Int J Cancer 1995, 60:539–544.

    Article  CAS  PubMed  Google Scholar 

  17. • Bartlett NL, Younes A, Carabasi MH, et al.: A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood 2008, 111:1848–1854. This phase 1 trial of a monoclonal anti-CD30 antibody demonstrated that SGN-30 is well tolerated and has modest clinical activity in patients with CD30+ lymphomas.

    Article  CAS  PubMed  Google Scholar 

  18. •• Forero-Torres A, Leonard JP, Younes A, 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, 146:171–179. This is a phase 2 study with 38 patients with refractory or relapsed HL. No objective responses were reported in HL, but 11 patients (29%) had stable disease.

    Article  CAS  PubMed  Google Scholar 

  19. Wahl AF, Klussman K, Thompson JD, et al.: The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res 2002, 62:3736–3742.

    CAS  PubMed  Google Scholar 

  20. Blum KA, Johnson JL, Jung S-H, et al.: Serious pulmonary toxicity with SGN-30 and gemcitabine, vinorelbine, and liposomal doxorubicin in patients with relapsed/refractory Hodgkin lymphoma (HL): Cancer and Leukemia Group B (CALGB) 50502 [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:Abstract 232.

  21. • Blum KA, Jung S-H, Johnson JL, et al.: Serious pulmonary toxicity in patients with Hodgkin’s lymphoma treated with the anti-CD30 antibody, SGN-30, and gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) is associated with a FcγRIIIa-158 V/F polymorphism: results from CALGB 50502. Ann Oncol, in press. SGN-30 cannot be safely administered in combination with GVD. Severe pulmonary toxicities were reported in patients with a V/F polymorphism in the FcγRIIa gene.

  22. Bartlett NL, Niedzwiecki D, Johnson JL, et al.: Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol 2007, 18:1071–1079.

    Article  CAS  PubMed  Google Scholar 

  23. • Ansell SM, Horwitz SM, Engert A, 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, 25:2764–2769. MDX-060 (5F11, anti-CD30 monoclonal antibody) was well tolerated but showed limited activity (ORR, 8%) in CD30+ lymphomas.

    Article  CAS  PubMed  Google Scholar 

  24. Ansell S, Horwitz S, Engert A, et al.: Increased doses of an anti-CD30 antibody, MDX-060, results in prolonged progression free survival in subjects with CD30 positive lymphoma [abstract]. AACR Meeting Abstracts 2008:Abstract 5525.

  25. A phase II study of MDX-060 in subjects with relapsed or refractory Hodgkin’s disease. ClinicalTrials.gov identifier: NCT00284804. Available at http://clinicaltrials.gov/. Accessed April 2010.

  26. Wu J, Edberg JC, Redecha PB, et al.: A novel polymorphism of FcγRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 1997, 100:1059–1070.

    Article  CAS  PubMed  Google Scholar 

  27. Koene HR, Kleijer M, Algra J, et al.: Fc γRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc γRIIIa, independently of Fc γRIIIa-48L/R/H phenotype. Blood 1997, 90:1109–1114.

    CAS  PubMed  Google Scholar 

  28. Niwa R, Natsume A, Uehara A, et al.: IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides. J Immunol Methods 2005, 306:151–160.

    Article  CAS  PubMed  Google Scholar 

  29. Cardarelli PM, Moldovan-Loomis MC, Preston B, et al.: In vitro and in vivo characterization of MDX-1401 for therapy of malignant lymphoma. Clin Cancer Res 2009, 15:3376–3383.

    Article  CAS  PubMed  Google Scholar 

  30. • Thertulien R, Frankel AE, Evens AM, et al.: A Phase I, open-label, dose-escalation, multidose study of MDX-1401 (defucosylated human antiCD30 monoclonal antibody) in patients with CD30-positive refractory/relapsed Hodgkin’s lymphoma [abstract]. AACR Meeting Abstracts 2009:Abstract 1227. This is a report of an ongoing phase 1 trial of a second-generation antibody derived from MDX-060. Preliminary results indicate that 8 of 12 patients had stable disease, but no objective responses have been reported.

  31. Hammond PW, Vafa O, Jacinto J, et al.: A humanized anti-CD30 monoclonal antibody, XmAbTM2513, with enhanced in vitro potency against CD30-positive lymphomas mediated by high affinity Fc-receptor binding [abstract]. Blood (ASH Annual Meeting Abstracts) 2005, 106:Abstract 1470.

  32. Lawrence CE, Hammond PW, Zalevsky J, et al.: XMAbTM2513, an Fc engineering humanized anti-CD30 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating hematologic malignancies [abstract]. Blood (ASH Annual Meeting Abstracts) 2007, 110:Abstract 2340.

  33. Blum KA, Smith M, 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 [abstract]. J Clin Oncol (ASCO Annual Meeting Abstracts) 2009, 27:15s, Abstract 8531.

    Google Scholar 

  34. Younes A: Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2009:507–519.

  35. Falini B, Bolognesi A, Flenghi L, et al.: Response of refractory Hodgkin’s disease to monoclonal anti-CD30 immunotoxin. Lancet 1992, 339:1195–1196.

    Article  CAS  PubMed  Google Scholar 

  36. Schnell R, Staak O, Borchmann P, et al.: 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 Can Res 2002, 8:1779–1786.

    CAS  Google Scholar 

  37. Dubowchik GM, Firestone RA, Padilla L, et al.: Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: model studies of enzymatic drug release and antigen-specific in vitro anticancer activity. Bioconjug Chem 2002, 13: 855–869.

    Article  CAS  PubMed  Google Scholar 

  38. Doronina SO, Toki BE, Torgov MY, et al.: Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 2003, 21:778–784.

    Article  CAS  PubMed  Google Scholar 

  39. Hamblett KJ, Senter PD, Chace DF, et al.: Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 2004, 10:7063–7070.

    Article  CAS  PubMed  Google Scholar 

  40. Sun MM, Beam KS, Cerveny CG, et al.: Reduction-alkylation strategies for the modification of specific monoclonal antibody disulfides. Bioconjug Chem 2005, 16:1282–1290.

    Article  CAS  PubMed  Google Scholar 

  41. McDonagh CF, Turcott E, Westendorf L, et al.: Engineering antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Protein Eng Des Sel 2006, 19:299–307.

    Article  CAS  PubMed  Google Scholar 

  42. Oflazoglu E, Kissler JM, Sievers EL, et al.: Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma. Br J Haematol 2008, 142:69–73.

    Article  CAS  PubMed  Google Scholar 

  43. Younes A, Forero-Torres A, Bartlett NL, et al.: Objective responses in a phase I dose-escalation study of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in patients with relapsed or refractory Hodgkin lymphoma [abstract]. J Clin Oncol (ASCO Annual Meeting Abstracts) 2008, 26:Abstract 8531.

  44. •• Younes A, Forero-Torres A, Bartlett NL, et al.: Multiple complete responses in a phase 1 dose-escalation study of the antibody-drug conjugate SGN-35 in patients with relapsed or refractory CD30-positive lymphomas [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:Abstract 1006. This phase 2 trial of antibody-drug conjugate SGN-35 (SGN-30 conjugated to monomethyl auristatin E) given every 3 weeks reveals durable objective responses (36% of HL patients) and tumor regression (86% of all patients). At doses of 1.2 mg/kg or higher, objective responses were reported in 50% of HL patients.

  45. •• Fanale M, Bartlett NL, Forero-Torres A, et al.: The antibody-drug conjugate brentuximab vedotin (SGN-35) induced multiple objective responses in patients with relapsed or refractory CD30-positive lymphomas in a phase 1 weekly dosing study [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:Abstract 2731. Weekly dosing of SGN-35 resulted in 52% of HL patients (17 of 33) achieving an objective response, with 9 CRs (27%). Grade III neuropathies emerged in 10% of patients after treatment at higher dose levels.

  46. A phase 1 study of brentuximab vedotin combined with ABVD for Hodgkin lymphoma. ClinicalTrials.gov identifier: NCT01060904. Available at http://clinicaltrials.gov/. Accessed April 2010.

  47. A pivotal open-label trial of SGN-35 for Hodgkin lymphoma. ClinicalTrials.gov identifier: NCT00848926. Available at http://clinicaltrials.gov/. Accessed April 2010.

  48. A phase 3 study of brentuximab vedotin (SGN-35) for prevention of hodgkin lymphoma progression (The AETHERA Trial). ClinicalTrials.gov identifier: NCT01100502. Available at http://clinicaltrials.gov/. Accessed April 2010.

  49. Huhn M, Sasse S, Tur MK, et al.: Human angiogenin fused to human CD30 ligand (Ang-CD30L) exhibits specific cytotoxicity against CD30-positive lymphoma. Cancer Res 2001, 61:8737–8742.

    CAS  PubMed  Google Scholar 

  50. Menzel C, Schirrmann T, Konthur Z, et al.: Human antibody RNase fusion protein targeting CD30+ lymphomas. Blood 2008, 111:3830–3837.

    Article  CAS  PubMed  Google Scholar 

  51. Schnell R, Dietlein M, Staak JO, et al.: Treatment of refractory Hodgkin’s lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol 2005, 23:4669–4678.

    Article  CAS  PubMed  Google Scholar 

  52. Zhang M, Yao Z, Patel H, et al.: Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1. Proc Natl Acad Sci U S A 2007, 104:8444–8448.

    Article  CAS  PubMed  Google Scholar 

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Disclosure

Dr. Bartlett received research funding from Seattle Genetics to conduct clinical trials of brentuximab vedotin. No other potential conflicts of interest relevant to this article were reported.

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  1. Washington University School of Medicine, Siteman Cancer Center, 660 South Euclid, Box 8056, St. Louis, MO, 63110, USA

    Kelley V. Foyil & Nancy L. Bartlett

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  2. Nancy L. Bartlett
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Correspondence to Nancy L. Bartlett.

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Foyil, K.V., Bartlett, N.L. Anti-CD30 Antibodies for Hodgkin Lymphoma. Curr Hematol Malig Rep 5, 140–147 (2010). https://doi.org/10.1007/s11899-010-0053-y

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