Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas

EA Demina

NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Elena Andreevna Demina, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7 (499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-398-405


ABSTRACT

The concept of total curability of Hodgkin’s lymphoma was introduced as early as in 1970s. However, 10–30 % of patients develop relapses; in addition, resistant tumors cannot be excluded. A high-dose chemotherapy with autologous hematopoietic stem cell transplantation is a modern treatment standard for relapses and refractory Hodgkin’s lymphomas. However, long-term remissions are achieved only in a half of these patients. The toxicity of effective first-line treatment regimens and insufficient effectiveness of regimens prescribed for relapses and refractory disease are the reason for further search of new therapeutic options for this malignant tumor. Invention of an immunoconjugate, brentuximab vedotin, became one of the new steps in the treatment of Hodgkin’s lymphomas. This review presents data on the pharmacological properties of the drug, the mechanism of the anti-tumor effect, as well as results of large international, randomized clinical trials.

Keywords: brentuximab vedotin, Hodgkin’s lymphoma, relapse, treatment.

Received: June 14, 2016

Accepted: June 17, 2016

Read in PDF (RUS) pdficon


REFERENCES

  1. De Vita VT. The consequences of the chemotherapy of Hodgkin’s disease: the 10th David A. Karnofsky memorial lecture. Cancer. 1981;47(1):1–13. doi: 10.1002/1097-0142(19810101)47:1<1::AID-CNCR2820470102>3.0.co;2-2.
  2. Engert A, Younes A, eds. Hematologic malignancies: Hodgkin lymphoma. 2nd edition. A Comprehensive Update on Diagnostics and Clinics. Berlin Heidelberg: Springer; 2015. doi: 10.1007/978-3-319-12505-3.
  3. Horning S, Fanale M, deVos S, et al. Defining a population of Hodgkin lymphoma patients for novel therapeutics: An international effort. Ann Oncol. 2008;19(Suppl 4): Abstract 118.
  4. Falini B, Pileri S, Pizzolo G, et al. 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):1–14.
  5. Matsumoto K, Terakawa M, Miura K, et al. Extremely rapid and intense induction of apoptosis in human eosinophils by anti-CD30 antibody treatment in vitro. J Immunol. 2004;172(4):2186–93. doi: 10.4049/jimmunol.172.4.2186.
  6. 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(19):2764–9. doi: 10.1200/jco.2006.07.8972.
  7. 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(2):171–9. doi: 10.1111/j.1365-2009.07740.x.
  8. Dosio F, Brusa P and Cattel L Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components. 2011;3(12):848–83. doi: 10.3390/toxins3070848.
  9. Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti-CD30–monomethyl auristatin E conjugate with potent and selective antitumor activity. 2003;102(4):1458–65. doi: 10.1182/blood-2003-01-0039.
  10. Sutherland MSK, Sanderson RJ, Gordon KA, et al. Lysosomal Trafficking and Cysteine Protease Metabolism Confer Target-specific Cytotoxicity by Peptide-linked Anti-CD30-Auristatin Conjugates. J Biol Chem. 2006;281(15):10540–7. doi: 10.1074/jbc.M510026200.
  11. Katz J, Janik JA, Yones A. Brentuximab vedotin (SGN-35). Clin Cancer Res. 2011;17(20):6428–36. doi: 10.1158/1078-0432.CCR-11-0488.
  12. Chen R, Gopal AK, Smith SE, et al. Five-year survival data demonstrating durable responses from a pivotal phase 2 study of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015;126(Suppl 23): Abstract 2736. doi: 10.1182/blood-2016-02-699850.
  13. Gardai SJ, Epp A, Law C-L. Brentuximab vedotin-mediated immunogenic cell death. Cancer Res. 2015;75(15): Abstract 2469. doi: 10.1158/1538-7445.am2015-2469.
  14. Oflazoglu E, Stone IJ, Gordon KA. Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30. Blood. 2007;110(13):4370–2. doi: 10.1182/blood-2007-06-097014.
  15. Fu L, Xinqun Z, Kim E, et al. Relationship between in vivo antitumor activity of ADC and payload release in preclinical models. Cancer Res. 2014;74(19): Abstract 3694. doi: 10.1158/1538-am2014-3694.
  16. Kim YH, Tavallaee M, Sundram U, et al. Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sezary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. J Clin Oncol. 2015;33(32):3750–8. doi: 10.1200/jco.2014.60.3969.
  17. Younes A, Gopal AK, Smith SE, 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.
  18. Arai S, Fanale M, DeVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell Leuk Lymphoma. 2013;54(11):2531–3. doi: 10.3109/10428194.2013.798868.
  19. Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(8):1236–43. doi: 10.1182/blood-2014-08-595801.
  20. Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol. 2006;24(10):1633–42. doi: 10.1200/jco.2005.04.0543.
  21. Swain SM, Arezzo JC. Neuropathy associated with microtubule inhibitors: Diagnosis, incidence, and management. Clin Adv Hematol Oncol. 2008;6(6):455–67.
  22. Zinzani PL, Corradini P, Gianni AM, et al. Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position Paper. Clin Lymph Myel Leuk. 2015;15(9):507–13. doi: 10.1016/j.clml.2015.06.008.
  23. Rothe A, Sasse S, Goergen H, et al. Brentuximab vedotin for relapsed or refractory CD30 hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012;120(7):1470–2. doi: 10.1182/blood-2012-05-430918.
  24. Gibb A, Jones C, Bloor A, et al. Brentuximab vedotin in refractory CD30 lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013;98(4):611–4. doi: 10.3324/haematol.2012.069393.
  25. Zinzani PL, Viviani S, Anastasia A, et al. Brentuximab vedotin in relapsed/refractory Hodgkin’s lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials. Haematologica. 2013;98(8):1232–6. doi: 10.3324/haematol.2012.083048.
  26. Perrot A, Monjanel H, Bouabdallah R, et al. Brentuximab vedotin as single agent in refractory or relapsed CD30-positive Hodgkin lymphoma: the French name patient program experience in 241 patients. Haematologica. 2014;99(s1):498, abstr. S1293.
  27. Perrot A, Monjanel H, Bouabdallah R, et al. Lymphoma Study Association (LYSA). Impact of post-brentuximab vedotin consolidation on relapsed/refractory CD30+ Hodgkin lymphomas: a large retrospective study on 240 patients enrolled in the French Named-Patient Program. 2016;101(4):466–73. doi: 10.3324/haematol.2015.134213. Epub 2016 Jan 14.
  28. Moskowitz CH, Yahalom J, Zelenetz AD, et al. High-Dose Chemo-Radiotherapy for Relapsed or Refractory Hodgkin Lymphoma and the Significance of Pre-transplant Functional Imaging. Br J Haematol. 2010;148(6):890–7. doi: 10.1111/j.1365-2141.2009.08037.x.
  29. Moskowitz AJ, Schoder H, Gerecitano JF. FDG-PET Adapted Sequential Therapy with Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant for Relapsed and Refractory Hodgkin Lymphoma. Blood (ASH Annual Meeting Abstracts). 2013;122(21): Abstract 2099.
  30. Moskowitz AJ, Hamlin PA Jr, Perales M-A, et al. Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2013;31(4):456–60. doi: 10.1200/jco.2012.45.3308.
  31. LaCasce A, Sawas A, Bociek RG, et al. A phase 1/2 single-arm, open-label study to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for patients with Hodgkin lymphoma in the first salvage setting: interim results. Biol Blood Marrow Transplant. 2014;20(2):S161. doi: 10.1016/j.bbmt.2013.12.257.
  32. Aparicio J, Segura A. Garcera S, et al. ESHAP is an Active Regimen for Relapsing Hodgkin’s Disease. Ann Oncol. 1999;10(5):593–5. doi: 10.1023/A:1026454831340.
  33. Garcia-Sanz R, Sureda A, Alonso-Alvarez S, et al. Evaluation of the Regimen Brentuximab Vedotin Plus ESHAP (BRESHAP) in Refractory or Relapsed Hodgkin Lymphoma Patients: Preliminary Results of a Phase I-II Trial from the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood. 2015: Abstract 582.
  34. Bartlett NL, Chen R, Fanale MA, et al. Retreatment with brentuximab vedotin in CD30-positive hematologic malignancies. J Hematol Oncol. 2014;7(1):24. doi: 10.1186/1756-8722-7-24.
  35. Batlevi CL, Younes A. Novel therapy for Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program. 2013;2013(1):394–9. doi: 10.1182/asheducation-2013.1.394.
  36. Majhail NS, Weisdorf DJ, Defor TE, et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin’s lymphoma. Biol Blood Marrow Transplant. 2006;12(10):1065–72. doi: 10.1016/j.bbmt.2006.06.006.
  37. Moskowitz CH, Paszkiewicz-Kozik E, Nadamanee A, et al. Analysis of primary-refractory Hodgkin lymphoma pts in a randomized, placebo-controlled study of brentuximab vedotin consolidation after autologous stem cell transplant. Hematol Oncol. 2015;33:165, abstr. 120.
  38. Moskowitz CH, Nademanee A, Masszi T, et 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(9980):1853–62. doi: 10.1016/S0140-6736(15)60165-9.
  39. Walewski JA, Nademanee A, Masszi T, et al. Multivariate analysis of PFS from the AETHERA trial: a phase 3 study of brentuximab vedotin consolidation after autologous stem cell transplant for HL. J Clin Oncol. 2015;33(Suppl): Abstract 8519.
  40. Sweetenham JW, Walewski J, Nadamanee A, et al. Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse. Biol Blood Marrow Transplant. 2016;22(3):S19e–S481, abstr. 24. doi: 10.1016/j.bbmt.2015.11.315.
  41. Bonthapally V, Ma E, Viviani S, et al. Healthcare utilization in the AETHERA trial: phase 3 study of brentuximab vedotin in patients at increased risk of residual Hodgkin lymphoma post-ASCT. Hematol Oncol. 2015;33:193, abstr. 177.
  42. Kuruvilla J, Connors JM, Sawas A, et al. A phase 1 study of brentuximab vedotin (BV) and bendamustine (B) in relapsed or refractory Hodgkin lymphoma (HL) and anaplastic large T-cell lymphoma (ALCL). Hematol Oncol. 2015;33:148, abstr. 090.
  43. Theurich S, Malcher J, Wennhold K, et al. Brentuximab Vedotin Combined With Donor Lymphocyte Infusions for Early Relapse of Hodgkin Lymphoma After Allogeneic Stem-Cell Transplantation Induces Tumor-Specific Immunity and Sustained Clinical Remission. J Clin Oncol. 2013;31(5):e59–e63. doi: 10.1200/jco.2012.43.6832.
  44. Vaklavas C, Forero-Torres A. Safety and efficacy of brentuximab vedotin in patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Ther Adv Hematol. 2012;3(4):209–25. doi: 10.1177/2040620712443076.