98 • Clinical Lymphoma September 2004 Yttrium 90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Produces High Response Rates and Durable Remissions in Patients with Previously Treated B-Cell Lymphoma Leo I. Gordon, 1 Thomas Witzig, 2 Arturo Molina, 3 Myron Czuczman, 4 Christos Emmanouilides, 5 Robin Joyce, 6 Katie Vo, 3 Charles Theuer, 3 Brad Pohlman, 7 Nancy Bartlett, 8 Greg Wiseman, 2 Mohamed Darif, 3 Christine White 3 We report updated time-to-event variables of a phase III randomized study comparing yttrium 90–labeled ibritumomab with rituximab stan- dard therapy in 143 rituximab-naive patients with relapsed or refractory low-grade, follicular, or transformed CD20 + non-Hodgkin’s lymphoma (NHL). Most patients (79%) had follicular lymphoma. Patients were randomized to receive a single intravenous (I.V.) dose of 90 Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m 2 I.V. weekly for 4 doses (n = 70). The radioimmunotherapy group was pretreated with 2 rituximab doses (250 mg/m 2 ) to improve biodistribution and one dose of Indium 111-labeled ibritumomab tiuxetan for imaging. The over- all response rate was 80% versus 56% (P = 0.002) and complete response (CR)/CR unconfirmed (CRu) rates were 34% for 90 Y ibritumomab tiuxetan versus 20% for rituximab. With a median follow-up of 44 months, the data are mature as all ongoing patients in both groups exceed- ed the median Kaplan-Meier estimated time to progression (TTP), duration of response (DR), and time to next therapy. Although this study was not powered to detect differences in time-to-event variables, the results from this randomized trial demonstrate trends toward longer median TTP (15 vs. 10.2 months; P = 0.07), DR (16.7 vs. 11.2 months; P = 0.44) and time to next therapy (21.1 vs. 13.8 months; P = 0.27) in follicular NHL patients treated with 90 Y ibritumomab tiuxetan compared with the rituximab control arm. In patients achieving a CR/CRu, the median TTP was 24.7 months for patients treated with 90 Y ibritumomab tiuxetan compared with 13.2 months for rituximab-treated patients (P = 0.41), and ongoing responses of > 5 years have been observed. These results confirm that 90 Y ibritumomab tiuxetan produces high response rates and durable remissions in patients with previously treated low-grade, follicular, and transformed NHL. Clinical Lymphoma, Vol. 5, No. 2, 98-101, 2004 Key words: Biodistribution, Follicular lymphoma, Non-Hodgkin’s lymphoma, Rituximab Abstract Original Contribution Introduction The efficacy and safety of radioimmunotherapy with yttrium 90–labeled tiuxetan for the treatment of patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL) have been confirmed in several clinical trials. 1-5 Among these trials is the randomized phase III study of radioimmunotherapy in NHL reported here, which is an evaluation of 90 Y ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy in rituximab-naive patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL. 3 The primary study goal was a comparison of overall response rates between treatment groups, with time to progression (TTP), duration of response (DR), and time to next anticancer therapy evaluated as secondary endpoints. The trial was powered to detect a 25% difference in overall response rate (ORR) between treatment groups, but not powered to detect a difference in TTP or other time to event variables. Results of the study were first reported in 2002. 3 A total of 143 patients were randomized to receive either a single Address for correspondence: Leo I. Gordon, MD, Division of Hematology/ Oncology, Northwestern University Feinberg School of Medicine, 676 N St. Clair, Suite 850, Chicago, IL 60611 Fax: 312-695-6189; l-gordon@northwestern.edu Submitted: Dec 10, 2003; Revised: Jan 29, 2004; Accepted: Feb 6, 2004. 1 Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 2 Mayo Clinic and Mayo Foundation, Rochester, MN 3 Biogen Idec Pharmaceuticals, San Diego, CA 4 Roswell Park Cancer Center, Buffalo, NY 5 Division of Hematology/Oncology, University of California, Los Angeles 6 Beth Israel Deaconess Medical Center, Boston, MA 7 The Cleveland Clinic Foundation, OH 8 Oncology Division, Washington University School of Medicine, St. Louis, MO Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-9655, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.