Journal of Clinical Oncology, Vol 20, Issue 15
(August), 2002: 3262-3269
© 2002 American Society for Clinical Oncology
Treatment With Ibritumomab Tiuxetan Radioimmunotherapy in Patients With Rituximab-Refractory Follicular Non-Hodgkin’s Lymphoma
By Thomas E. Witzig,
Ian W. Flinn,
Leo I. Gordon,
Christos Emmanouilides,
Myron S. Czuczman,
Mansoor N. Saleh,
Larry Cripe,
Gregory Wiseman,
Teresa Olejnik,
Pratik S. Multani,
Christine A. White
From the Mayo Clinic, Rochester, MN; Johns Hopkins Oncology Center, Baltimore, MD; Northwestern University/Robert H. Lurie Cancer Center, Chicago, IL; University of California, Los Angeles, and IDEC Pharmaceuticals Corporation, San Diego, CA; Roswell Park Cancer Institute, Buffalo, NY; University of Alabama, Birmingham, AL; and Indiana Cancer Pavilion, Indianapolis, IN.
Address reprint requests to Thomas E. Witzig, MD, 620 Stabile Bldg, Mayo Clinic, Rochester, MN 55905; email: witzig{at}mayo.edu
PURPOSE: Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin’s lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL.
PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m2 weekly for 4 weeks) or time to progression (TTP) of  6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m2 intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients.
RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors  5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier–estimated TTP was 6.8 months (range, 1.1 to 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively.
CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.
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