Brentuximab Vedotin in CD30-Positive Lymphoma

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In August 2011, the FDA granted an accelerated approval to brentuximab vedotin as a treatment for patients with systemic anaplastic large-cell lymphoma (ALCL) based on a single-arm clinical trial. This study enrolled 58 patients with CD30-positive systemic ALCL following front-line treatment with chemotherapy.

In the study, 86% of patients achieved an objective response (complete response = 57%; partial response = 29%). In addition to response rates, a plateau in progression-free survival and overall survival is evident for some patients, Andrei R. Shustov, MD, suggests.

As a result of these responses, some patients are able receive a consolidative transplantation. However, more impressively, Shustov believes, are the elderly patients who refused consolidative therapy and respond to treatment with brentuximab for longer than 2 years.

At this point, it remains unclear whether brentuximab could be used as a maintenance therapy. Additionally, Shustov notes, the optimal number of treatment cycles to administer is unknown for patients who experience a complete response. Despite these concerns, studies have suggested that patients who stop taking the drug and then relapse will continue to respond to brentuximab when treatment is re-administered, Shustov states.

Brentuximab is also being explored as a treatment for patients with cutaneous T-cell lymphoma (CTCL), notes Lauren C. Pinter-Brown, MD. A phase II study in patients with relapsed or refractory mycosis fungoides with variable CD30 expression showed an objective response rate of 70%. This led to the initiation of a phase III study examining brentuximab versus physician’s choice in patients with CD30-positive CTCL, Pinter-Brown notes.

In the CTCL studies, CD30 expression was measured by IHC from biopsies of skin lesions. At this point, there doesn’t appear to be a correlation between IHC staining and response, Pinter-Brown suggests.

In a broad phase II study looking at patients with greater than 1% CD30 expression, there appeared to be high response rate in patients with angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified, Steve M. Horwitz, MD, notes. These studies found that patients who responded to brentuximab had elevated serum levels of soluble CD30. This data suggests that IHC may not be the most effective test for the detection of clinically meaningful CD30 positivity, Horwitz believes.