Phase I/II Trial of IDEC-Y2B8 Radioimmunotherapy for Treatment of Relapsed or Refractory CD20+B-Cell Non-Hodgkin's Lymphoma

作者：Thomas Elmer Witzig, Christine A. White, Gregory A. Wiseman, Leo I. Gordon, Christos E. Emmanouilides, Andrew Antony Raubitschek, Nalini Janakiraman, John C. Gutheil, Russell J. Schilder, STEWART M. SPIES, Daniel H.S. Silverman, Elizabeth U. Parker, Antonio J Grillo-López · 发表于：Journal of Clinical Oncology · 年份：1999 · DOI：10.1200/jco.1999.17.12.3793 · 被引用次数：541 · 研究领域：Lymphoma Diagnosis and Treatment、Radiopharmaceutical Chemistry and Applications、Monoclonal and Polyclonal Antibodies Research

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm. RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily he...