Phase II Brentuximab Vedotin Trial for Relapsed or Refractory High-CD30-Expressing Non-Hodgkin Lymphomas

Abstract

Background: The treatment outcome of Brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. This study explored the efficacy of BV in high-CD30-expressing non-Hodgkin lymphoma (NHL) patients, excluding those with other than anaplastic large cell lymphoma (ALCL). As CD30 expression is associated with Epstein-Barr virus (EBV) infection and multiple myeloma oncogene-1 (MUM1) expression of tumor cells, we also performed a post-hoc analysis for their association with outcome of BV. Methods: This phase II study enrolled relapsed or refractory high-CD30-expressing NHL, other than ALCL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease, after a maximum of 16 cycles of BV. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry. Findings: In total, 33 patients were enrolled, with diffuse large B-cell lymphoma (n=12), peripheral T-cell lymphoma (n=8), extranodal NK/T-cell lymphoma (n=7), primary mediastinal large B-cell lymphoma (n=3), transformed mycosis fungoides (n=2), and angioimmunoblastic T-cell lymphoma (n=1). The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV was not significantly associated with the extent of patients' CD30 expression. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. Survival did not differ based on the extent of CD30 expression or subtype. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). Post hoc analyses of the associations between MUM1 and outcomes showed a higher response among MUM1-negative patients (55.6%, 5/9) compared with MUM1-positive patients (13.3%, 2/15). Interpretation: BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles in relapsed or refractory high-CD30-expressing NHL patients, especially MUM1-negative patients. MUM1 negativity may be a biomarker predicting response to BV. Clinical Trial Registration Number: (Clinicaltrials.gov identifier: NCT02280785) Funding Statement: Takeda Pharmaceutical Company Limited Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The Institutional Review Board of each participating institute approved this study.