Originally published as JCO Early Release 10.1200/JCO.2005.12.171 on January 18 2005

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Phase II Trial of Individualized Rituximab Dosing for Patients With CD20-Positive Lymphoproliferative Disorders

From the Division of Hematology/Oncology, Department of Medicine; Division of Hematopathology, Department of Pathology; Department of Radiation Oncology; University of Florida College of Medicine and Shands Cancer Center, Gainesville, FL

Address reprint requests to James W. Lynch, MD, Box J-100277 JHMHC, 1600 SW Archer Road, Division of Hematology/Oncology, UF College of Medicine, Gainesville, FL 32610; e-mail: lynchjw{at}medicine.ufl.edu

PURPOSE: To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule.

PATIENTS AND METHODS: Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m². All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m² when the level decreased below 25 µg/mL.

RESULTS: Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range.

CONCLUSION: Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m² of rituximab every 3 to 4 months.

Supported in part by a grant from Genentech Inc, South San Francisco, CA.

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

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