Originally published as JCO Early Release 10.1200/JCO.2005.01.0892 on October 3 2005

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Re-Treatment With I-131 Tositumomab in Patients With Non-Hodgkin's Lymphoma Who Had Previously Responded to I-131 Tositumomab

From the University of Michigan Medical Center, Ann Arbor, MI; Christie Hospital, Manchester, UK; Rush-Presbyterian-St Luke's Medical Center, Chicago, IL; The New York Hospital-Cornell Medical Center, New York, NY; Stanford University Medical Center, Stanford, CA; Corixa Corporation, Seattle, WA; and Johns Hopkins School of Medicine, Baltimore, MD

Address reprint requests to Mark S. Kaminski, MD, University of Michigan Comprehensive Cancer Center, 1500 E Medical Center Drive, Room 4316, Cancer Center, Ann Arbor, MI; e-mail: mkaminsk{at}umich.edu

PURPOSE: To study efficacy and safety of re-treatment with I-131 tositumomab in patients with low-grade, follicular, or transformed low-grade B-cell lymphoma who relapsed following a response to I-131 tositumomab.

PATIENTS AND METHODS: A prior response 3 months to I-131 tositumomab was required. The single therapeutic dose following a dosimetric dose was adjusted to give the same total body dose (in Gy) as that used for the original dose, or was attenuated if the platelet count was less than 150,000 per mm³ or if the prior treatment resulted in grade 4 cytopenias lasting longer than 7 days.

RESULTS: Of 32 patients enrolled, 28 completed the therapeutic dose. A median of four therapies were given before re-treatment. Eighteen (56%) of 32 patients had a complete or partial response (median duration, 15.2 months); eight (25%) had a complete response (median duration, 35 months). Five continue in response from 1.8 to 5.7 years, with a median follow-up of 35 months. The overall median response duration was not significantly different for the two treatments, with no clinical factors predicting response or its duration. Ten of 18 re-responders had longer responses with re-treatment, with five having responses 1.5 years longer. Grade 3/4 neutropenia and thrombocytopenia occurred in 50% and 43% of patients, respectively, similar to initial treatment. Antimouse antibodies developed in 10% of patients, and 12% developed elevated serum thyroid-stimulating hormone. Six patients were diagnosed with second malignancies, including four patients who developed myelodysplastic syndrome (one who had not received the therapeutic dose) and one with acute myelogenous leukemia.

CONCLUSION: Re-treatment with I-131 tositumomab following a previous response can produce second responses that can be durable.

Supported by Corixa and GlaxoSmithKline, who have provided collaborative support and assistance to the authors for the research, writing, and production of this manuscript.

Presented in part as a poster at the 45th Annual Meeting and Exposition of the American Society of Hematology, San Diego, CA, December 6, 2003.

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

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