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

TLDR

Brentuximab vedotin is an antibody‑drug conjugate that delivers monomethyl auristatin E to CD30‑positive cells and showed significant activity with a favorable safety profile in phase I trials of relapsed or refractory CD30‑positive lymphomas. The study aimed to evaluate the efficacy and safety of brentuximab vedotin in relapsed or refractory Hodgkin’s lymphoma patients after autologous stem‑cell transplantation. Patients with histologically confirmed CD30‑positive HL received 1.8 mg/kg brentuximab vedotin intravenously every three weeks for up to 16 cycles. The treatment achieved a 75 % overall objective response rate (34 % complete remissions), median progression‑free survival of 5.6 months, durable responses lasting up to 20.5 months, manageable toxicity, and 31 patients progression‑free after more than 1.5 years.

Abstract

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.