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Abbreviated Chemotherapy With Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma

From the Center for Lymphoma and Myeloma, Division of Hematology and Medical Oncology, Division of Nuclear Medicine, and Department of Pathology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY; and Corixa Corporation, Seattle, WA

Address reprint requests to John P. Leonard, MD, Starr Bldg Rm 340, Weill Medical College of Cornell University and New York Presbyterian Hospital, 520 E 70th St, New York, NY 10021; e-mail: jpleonar{at}med.cornell.edu

PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma.

PATIENTS AND METHODS: Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab.

RESULTS: After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT.

CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.

Supported by K23 award No. RR16814 from the National Institutes of Health, and grants from the Cornell Center for Aging Research and Clinical Care, the Lymphoma Research Foundation, the Dorothy Rodbell Cohen Foundation, and the Brian Rooney Fund of the Lymphoma Foundation, as well as research grants from Corixa Corporation.

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

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