Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma

• Published in: Journal of clinical oncology Vol. 30; no. 18; pp. 2183 - 2189
• Main Authors: Younes, Anas, Gopal, Ajay K., Smith, Scott E., Ansell, Stephen M., Rosenblatt, Joseph D., Savage, Kerry J., Ramchandren, Radhakrishnan, Bartlett, Nancy L., Cheson, Bruce D., de Vos, Sven, Forero-Torres, Andres, Moskowitz, Craig H., Connors, Joseph M., Engert, Andreas, Larsen, Emily K., Kennedy, Dana A., Sievers, Eric L., Chen, Robert
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.06.2012
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Hodgkin Disease - drug therapy; Humans; Immunoconjugates - adverse effects; Immunoconjugates - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; ORIGINAL REPORTS; Recurrence; Tumors; Young Adult; Human; Relapse; Treatment resistance; Cancerology; Treatment; Lymphoproliferative syndrome; Phase II trial; Hodgkin disease; Malignant hemopathy; Lymphoma; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2011.38.0410

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas. In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility. The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.