Role of brentuximab vedotin in the treatment of relapsed or refractory Hodgkin lymphoma

Abstract

Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30-positive malignancies via an anti-CD30 monoclonal antibody linked to monomethyl auristatin E, a microtubule-disrupting agent, by a protease-cleavable linker. BV has received accelerated approval from the US Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in patients ineligible for ASCT, and in systemic anaplastic large cell lymphoma after failure of at least one line of multiagent chemotherapy. Phase I studies in CD30-positive lymphomas have determined the maximum tolerated dose to be 1.8 mg/kg intravenously every 21 days. In relapsed/refractory Hodgkin lymphoma, a pivotal Phase II study of single-agent BV showed an overall response rate of 75%, with 34% complete responses and a median remission duration of 20 months for complete responders. BV has a modest toxicity profile, with peripheral neuropathy as one of the most clinically significant side effects, and this is largely reversible. Therefore, BV is the treatment of choice for patients with relapsed/refractory Hodgkin lymphoma after ASCT or two standard regimens. Ongoing trials are evaluating the role of BV as salvage therapy prior to ASCT and for maintenance after ASCT for patients with relapsed/refractory disease.

Keywords: CD 30; Hodgkin lymphoma; antibody-drug conjugate; brentuximab vedotin.

Figure 1

Mechanism of action of brentuximab vedotin. Abbreviation: HRS, Hodgkin Reed Sternberg.