Originally published as JCO Early Release 10.1200/JCO.2008.19.2245 on March 2 2009

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Yttrium-90 Ibritumomab Tiuxetan Doses Calculated to Deliver up to 15 Gy to Critical Organs May Be Safely Combined With High-Dose BEAM and Autologous Transplantation in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

From the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL; Division of Hematology and Diagnostic Radiology, Mayo Clinic, Rochester, MN; Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and Medical Research, Biogen Idec, San Diego, CA.

Corresponding author: Jane N. Winter, MD, Division of Hematology/Oncology, Feinberg School of Medicine, 676 N St Clair St, Ste 850, Chicago, IL 60611; e-mail: j-winter{at}northwestern.edu.

Purpose To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 (⁹⁰Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.

Patients and Methods Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized ⁹⁰Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of ⁹⁰Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.

Results Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.

Conclusion Dose-escalated ⁹⁰Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Supported in part by research funding from Biogen Idec (J.N.W. and D.J.I.) and by US Public Health Service Grant No. P30CA 060553 to Northwestern University.

Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 6-9, 2006, Orlando, FL; the Aggressive Lymphoma Workshop of the German High-Grade Lymphoma Study Group, September 12-14, 2007, Gottingen, Germany; the Annual Meeting of the American Society for Blood and Marrow Transplantation, February 13-15, 2004, Keystone, CO; and the 46th Annual Meeting of the American Society of Hematology, December 4-7, 2004, San Diego, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

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