Brentuximab Vedotin: A New Age in the Treatment of Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma

OBJECTIVE: To review the clinical trial data, pharmacology, pharmacokinetics, and adverse effects of brentuximab vedotin. DATA SOURCES: A literature search was performed using MEDLINE and PubMed (both 1966-October 2011), as well as the American Society of Hematology abstracts (2000-January 2012), using the primary search terms brentuximab vedotin, SGN35, Hodgkin lymphoma (HL), and anaplastic large cell lymphoma (ALCL). STUDY SELECTION AND DATA EXTRACTION: Published and ongoing clinical studies and abstracts in the English language that detail the pharmacology, pharmacokinetics, safety, and clinical efficacy of brentuximab vedotin in the treatment of HL and ALCL were included in this review. DATA SYNTHESIS: Brentuximab vedotin is an antibody drug conjugate that combines the anti-CD30 antibody, cAC10, with the synthetic tubulin disrupting agent monomethyl auristatin E. A Phase 1 trial in patients with relapsed and refractory HL or systemic ALCL supported a dose of 1.8 mg/kg every 3 weeks. The drug was well tolerated, with the majority of adverse reactions being grade 1 or 2 in severity. Common toxicities included fatigue, pyrexia, diarrhea, nausea, neutropenia, and peripheral neuropathy. Phase 2 studies in the same patient populations illustrated objective response rates of 73-86% with an acceptable toxicity profile. Based on results of these Phase 2 trials, the Food and Drug Administration granted approval of brentuximab vedotin in August 2011 for the treatment of relapsed and refractory HL or ALCL. CONCLUSIONS: Phase 1 and 2 clinical trial data indicate that brentuximab vedotin is efficacious and safe in patients with relapsed and refractory CD30-positive lymphomas. This agent is being investigated in combination with chemotherapy to further elucidate its role in lymphoma therapy.