Introduction: Antibody-Drug Conjugates in Lymphoma

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Moderator Myron S. Czuczman, MD, introduces a panel discussion focused on the current treatment landscape and emerging treatment trends for patients with lymphoid malignancies. The conversation includes expert perspectives from Steve M. Horwitz, MD, Lauren C. Pinter-Brown, MD, Andrei R. Shustov, MD, and Anas Younes, MD.

Recent advances in the linking technology utilized by antibody-drug conjugates (ADC) have markedly improved the effectiveness of this class of agents, remarks Czuczman. This advance was highlighted by the approval of the CD30-directed ADC brentuximab vedotin (Adcetris) in August 2011 for patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma (ALCL).

The linker technology is very important for the success of an ADC, notes Younes. The link must be stable enough that it is not cleaved in the serum or the plasma, so that it can deliver the payload without releasing the toxin in the blood. Brentuximab vedotin is a cleavable ADC that binds to CD30 and is then internalized. At that point, the link is degraded by the lysosome causing the release of the drug. Once released the drug is nonspecific, which creates a bystander effect. With noncleavable ADCs, the toxin remains attached to the antibody, minimizing this effect, Younes notes.

Brentuximab was approved based on response rate as a single agent in the relapsed setting for patients with Hodgkin lymphoma and ALCL. An approval based on response was sufficient for FDA approval, based on unmet medical need, Younes notes.

In addition to these indications, brentuximab vedotin is also being explored as a treatment for patients with diffuse large B-cell lymphoma (DLBCL) in the relapsed setting. A phase II study recently reported an objective response rate of 42% with a median duration of response of 11.5 months. This data showed that brentuximab vedotin is active in other types of CD30-positive lymphomas, Younes states.