Brentuximab Vedotin for Hodgkin Lymphoma and Systemic Anaplastic Large Cell Lymphoma: A Review of Clinical Experience and Future Directions

Abstract

SUMMARY Brentuximab vedotin is a novel agent indicated for the treatment of relapsed and refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Brentuximab vedotin is an antibody–drug conjugate consisting of chimeric anti-CD30 antibody cAC10, linked to four molecules of monomethylauristatin E, a tubulin destabilizer. It was granted US FDA approval in 2011 following two pivotal Phase II studies showing objective responses of 75 and 86% in heavily pretreated relapsed and refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, respectively. Brentuximab vedotin can be used as a bridge to more definitive stem cell transplant. There are currently over 30 open clinical studies involving the use of brentuximab vedotin used as single agent or combined with chemotherapy in both front-line and salvage settings. These studies include use in other CD30-positive B- and T-cell lymphomas, as well as in CD30-positive germ cell tumors. In clinical practice brentuximab vedotin has been associated with significant sensory and motor neuropathies and clinicians should be alert to the potential for significant neuropathy and the need for dose reduction. However, the potential for significant neuropathy must be balanced against the remarkable clinical benefit of brentuximab vedotin in patients with heavily pretreated relapsed and refractory lymphomas.