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

Abstract:

Treatment of primary refractory and relapsed classical Hodgkin lymphoma remains challenging, with disappointing results overall and only a minority of patients enjoying a longterm 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