Profile of brentuximab vedotin and its potential in the treatment of relapsed or refractory Hodgkin lymphoma

Sam Mayes,¹ Adam Gibb,¹ Tim Illidge<sup>1,2

1</sup>The Christie Hospital NHS Foundation, Wilmslow Road, ²School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Sciences Centre, UK

Abstract: Treatment of primary refractory and relapsed classical Hodgkin lymphoma remains challenging, with disappointing results overall and only a minority of patients enjoying a long-term cure. Until recently, antibody therapy has not played any role in the management of this form of Hodgkin lymphoma. The CD30 antigen was first identified in the Hodgkin Reed–Sternberg malignant cell of Hodgkin lymphoma and emerged as a promising potential target for antibody treatment. The first-generation monoclonal anti-CD30 antibodies proved disappointing with little clinical efficacy. More recently, a novel class of antibody-drug conjugates has emerged. Antibody-drug conjugates offer the potential to target tumor tissue more specifically and deliver potent drug therapies with minimal or less systemic toxicity. Brentuximab vedotin (SGN-35) is one such drug of this class and combines an anti-CD30 monoclonal antibody and the antitubulin agent, monomethyl auristatin E. Initial Phase I studies of brentuximab vedotin showed a promising 52% overall response rate in relapsed Hodgkin lymphoma, with minimal toxicity. More recently, the pivotal Phase II study in 102 patients demonstrated an overall response rate of 75% and a complete response rate of 34%. The median duration of response was 6.7 months, but this was extended to 20.5 months in those who achieved a complete response. This review outlines the development of the antibody-drug conjugate, brentuximab vedotin, for relapsed or refractory classical Hodgkin lymphoma.

Keywords: Hodgkin lymphoma, brentuximab vedotin, anti-CD30, antibody, conjugate