Brentuximab Vedotin in Hodgkin Lymphoma

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The FDA approved brentuximab vedotin as a treatment for patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma in August 2011. The approval in Hodgkin lymphoma was based on an objective response rate of 73%. The duration of response was 6.7 months and 32% of patients experienced a complete response. At the 2014 ASH Annual Meeting, findings from the phase III AETHERA study demonstrated a 2-year progression-free survival rate of 65% with brentuximab compared with 45% with placebo (HR = 0.50). Results from the AETHERA study will be submitted to the FDA as a post-marketing requirement.

Brentuximab is an antibody-drug conjugate whose antibody component binds to CD30, an antigen expressed on the surface of lymphoma cells, explains Robert Chen, MD. Once the conjugate binds to CD30, it is internalized into the cell where cytotoxic molecules are released and attack the microtubule network, causing cell arrest and apoptosis.

Following its approval, brentuximab quickly became the standard of care for patients with Hodgkin lymphoma who relapsed after autologous stem cell transplant or who received several lines of therapy and were ineligible for transplantation, explains John Sweetenham, MD. The therapy is being explored across a variety of settings due to its unique mechanism of action, high level of efficacy, and tolerable toxicity profile.

As a single-agent, brentuximab has demonstrated promising response rates in the salvage setting, Anas Younes, MD, explains. Ongoing clinical trials are investigating brentuximab in several settings, including its use alongside frontline therapy versus ABVD. A phase III study is currently comparing frontline brentuximab plus AVD (bleomycin omitted) versus ABVD for patients with Hodgkin lymphoma (NCT01712490).