Objective responses with brentuximab vedotin (SGN-35) retreatment in CD30-positive hematologic malignancies: A case series.

8062 Background: Brentuximab vedotin is an anti-CD30 antibody conjugated to the highly potent antitubulin agent, monomethyl auristatin E (MMAE), by a plasma-stable linker. Brentuximab vedotin selectively induces apoptosis in CD30+ cells by binding, internalizing, and releasing MMAE. In phase I clinical studies, good tolerability and antitumor activity were demonstrated in patients with CD30+ hematologic malignancies. This case series describes patients who have experienced relapse and were retreated with brentuximab vedotin. Methods: Heavily pretreated, relapsed or refractory patients with CD30+ hematologic malignancies have been retreated with brentuximab vedotin in 3 multicenter studies. Patients had SD with decreasing tumor volume or better (Cheson 2007) with prior brentuximab vedotin treatment, and subsequently experienced relapse. In their retreatment experiences, patients received brentuximab vedotin IV infusions of 1 mg/kg qweek or 1.8 mg/kg q3week, depending on the study. Results: Across these 3 studies, 7 patients had 8 retreatment experiences. Patients had either ALCL (1) or HL (6); ages ranged from 28–39 years. At baseline prior to retreatment, ECOG performance statuses were 0/1 (7), or 2 (1). Since the prior experience with brentuximab vedotin, the number of chemotherapy regimens was either 0 (4) or 1–3 (4), and 1 patient had an autologous stem cell transplant. Adverse events that occurred in more than 1 patient with retreatment were upper respiratory tract infection (3) and peripheral sensory neuropathy (2); all treatment-related AEs were G1/2 in severity. Among the retreatment experiences, there were 2 CR, 4 PR, and 2 SD; tumor regression was observed in all instances. All objective responses were observed 5–13 weeks after the start of retreatment, and retreatment response durations of 52+ weeks have been demonstrated. Conclusions: Retreatment with brentuximab vedotin was well tolerated. Objective responses were observed (6 of 8) with brentuximab vedotin retreatment in this heavily pretreated population. Enrollment to a phase 2 retreatment study in patients who previously experienced an objective response to brentuximab vedotin is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seattle Genetics, Inc. Seattle Genetics, Inc. Seattle Genetics, Inc.