A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Epstein-Barr Virus-Positive- and CD30-Positive Lymphomas

Abstract

Background: CD30 is frequently expressed in Epstein-Barr virus (EBV)-infected lymphoid cells and overexpressed in EBV-positive lymphomas. This open-labeled, multi-center, and investigator-initiated phase-II study evaluated the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas (NCT02388490). Methods: Twenty-five patients with relapsed or refractory EBV-positive lymphomas having CD30-positivity (≥ 1% of tumor cells) were administered with 1.8 mg/kg brentuximab vedotin intravenously every 3 weeks up to 16 cycles until disease progression. The primary endpoint was objective response rate and toxicities, duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were the secondary endpoints. Findings: Twenty-two patients (88%), median age of 65 years, were EBV-positive mature T/NK cell neoplasms (angioimmunoblastic T-cell lymphoma, n = 10; EBV-positive peripheral T-cell lymphoma, unspecified, n = 5; extranodal NK/T-cell lymphoma, nasal type, n = 4; and others, n = 3). Most patients (90%) had initial stage III/IV and 15 (60%) received ≥2 prior regimens. The objective response rate was 48% (90% CI, 31·0% to 64·3%; 12 of 25 patients), including five complete responses (20%) and seven partial responses (28%). Median DoR, PFS and OS were 10·1, 6·1, and 15·6 months, respectively. Common adverse events were peripheral neuropathy (48%), neutropenia (40%), thrombocytopenia (20%), and rashes (16%). Grade 3 and 4 adverse events were neutropenia (20%), thrombocytopenia (12%), and anemia (8%). Interpretation: Brentuximab vedotin is active and well tolerated in patients with relapsed or refractory EBV-positive and CD30-positive lymphomas. Trial Registration: (NCT02388490) Funding Statement: Takeda Pharmaceuticals Co. Ltd and Korea Health Industry Development Institute. Declaration of Interests: TMK received a research grant from AstraZeneca-KHIDI outside this work. DWK received travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi-Sankyo outside this work. All other authors declare no competing interests. Seoul National University Hospital received grants from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan. Ethics Approval Statement: The study was approved by the institutional review board at each participating site and written informed consent was obtained.