Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Fig 1.

Maximum percent reduction in the sum of the product of diameters in individual patients (n = 98) per Cheson et al. Tumor size reductions were observed in 96 (94%) of 102 patients. Four patients were not included in the analysis; three patients had no measurable lesions per independent review facility (IRF), and one patient had no postbaseline scans.

Fig 2.

Secondary end points of overall survival (A) and progression-free survival (B). ITT, intent to treat.

Fig 3.

Progression-free survival (PFS) achieved with brentuximab vedotin compared with PFS achieved with the last prior therapy. Data shown are median PFS as assessed by investigator in the subset of patients (n = 57) who received systemic therapy after autologous stem-cell transplantation and before receiving brentuximab vedotin.

Fig A1.

Progression-free survival of patients according to best response. CR, complete remission; PD, progressive disease; PR, partial remission; SD, stable disease.