Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma

详细信息    查看全文

• 作者：Andrew J. Cowan ; Phillip A. Stevenson ; Ted A. Gooley ; Shani L. Frayo ; George R. Oliveira ; Stephen D. Smith ; Damian J. Green ; Jennifer E. Roden ; John M. Pagel ; Brent L. Wood ; Oliver W. Press and Ajay K. Gopal
• 刊名：British Journal of Haematology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：176
• 期：4
• 页码：583-590
• 全文大小：326K
• ISSN：1365-2141

文摘

Fenretinide, a synthetic retinoid, induces apoptotic cell death in B-cell non-Hodgkin lymphoma (B-NHL) and acts synergistically with rituximab in preclinical models. We report results from a phase I-II study of fenretinide with rituximab for B-NHLs. Eligible diagnoses included indolent B-NHL or mantle cell lymphoma. The phase I design de-escalated from fenretinide at 900 mg/m² PO BID for days 1–5 of a 7-day cycle. The phase II portion added 375 mg/m² IV rituximab weekly on weeks 5–9 then every 3 months. Fenretinide was continued until progression or intolerance. Thirty-two patients were treated: 7 in phase I, and 25 in phase II of the trial. No dose-limiting toxicities were observed. The phase II component utilized fenretinide 900 mg/m² twice daily with rituximab. The most common treatment-related adverse events of grade 3 or higher were rash (n = 3) and neutropenia (n = 3). Responses were seen in 6 (24%) patients on the phase II study, with a median duration of response of 47 months (95% confidence interval, 2–56). The combination of fenretinide and rituximab was well tolerated, yielded a modest overall response rate, but with prolonged remission durations. Further study should focus on identifying the responsive subset of B-NHL.