Originally published as JCO Early Release 10.1200/JCO.2003.08.043 on February 20 2003

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Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin’s Lymphoma

Thomas E. Witzig, Christine A. White, Leo I. Gordon, Gregory A. Wiseman, Christos Emmanouilides, James L. Murray, John Lister, Pratik S. Multani

From the Division of Internal Medicine and Hematology and the Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN; IDEC Pharmaceuticals Corporation, San Diego, and University of California Los Angeles Medical Center, Los Angeles, CA; Division of Hematology/Oncology and The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; M.D. Anderson Cancer Center, Houston, TX; and Western Pennsylvania Cancer Institute, Pittsburgh, PA.

Address reprint requests to Thomas E. Witzig, MD, Mayo Clinic, 620 Stabile Building, Rochester, MN 55905; email: witzig{at}mayo.edu.

Purpose: Radioimmunotherapy (RIT) with yttrium-90 (⁹⁰Y)-labeled anti-CD20 antibody (⁹⁰Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with ⁹⁰Y ibritumomab tiuxetan.

Patients and Methods: Patients received rituximab 250 mg/m² on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of ⁹⁰Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease.

Results: Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment.

Conclusion: Single-dose ⁹⁰Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/µL, and neutrophils greater than 1,500 cells/µL.

Supported by grants from IDEC Pharmaceuticals Corporation, San Diego, CA.

Two of the authors (C.A.W. and P.S.M.) have declared a financial interest in a company whose product was studied in this article.

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