Combination of the anti‐CD30‐auristatin‐E antibody‐drug conjugate (SGN‐35) with chemotherapy improves antitumour activity in Hodgkin lymphoma

• Published in: British journal of haematology Vol. 142; no. 1; pp. 69 - 73
• Main Authors: Oflazoglu, Ezogelin, Kissler, Kim M., Sievers, Eric L., Grewal, Iqbal S., Gerber, Hans‐Peter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2008; Blackwell
• Subjects: ABVD; Animals; antibody‐drug conjugate; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bleomycin - administration & dosage; Dacarbazine - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Doxorubicin - administration & dosage; gemcitabine; Haematological Malignancy; Hematologic and hematopoietic diseases; Hodgkin Disease - therapy; Hodgkin lymphoma; Immunoconjugates - administration & dosage; Ki-1 Antigen - administration & dosage; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Mice, SCID; Neoplasm Transplantation; Oligopeptides - administration & dosage; SGN‐35; Tubulin Modulators - administration & dosage; Vinblastine - administration & dosage; Antineoplastic agent; Drug; Gemcitabine; Hematology; Antibody; Hodgkin disease; Malignant hemopathy; Lymphoma; Biological activity; ABVD; Chemotherapy; Treatment; antibody-drug conjugate; Antimetabolic; Lymphoproliferative syndrome; Pyrimidine derivatives; Fluorine Organic compounds; SGN-35; Pyrimidine nucleoside; Cancer; Hodgkin lymphoma
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2008.07146.x

Summary The antibody‐drug conjugate (ADC) cAC10‐vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti‐CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30‐positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large‐cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN‐35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or gemcitabine. Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL.