Final results of a phase I radioimmunotherapy trial using 186Re-epratuzumab for the treatment of patients with non-Hodgkin's lymphoma

Ernst J. Postema, John M M Raemaekers, Wim J G Oyen, Otto C. Boerman, Caroline M P W Mandigers, David M. Goldenberg, Guus A M S Van Dongen, Frans H M Corstens

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Abstract

Purpose: Radioimmunotherapy (RIT) is an effective, new treatment modality for non-Hodgkin's lymphoma (NHL). The aim of this study was to determine the maximum tolerated dose and a first impression of the therapeutic potential of 186Re-epratuzumab in patients with NHL. Experimental Design: Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received 99mTc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with 186Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m2. Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m2; otherwise three additional patients were included on that dose level. Results: A total of 18 patients received a diagnostic dose of 99mTc-epratuzumab. Fifteen patients were actually treated with 186Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m2. During or after infusion of 186Re-epratuzumab, no adverse reactions were seen. In all patients, a transient decrease of leukocyte and platelet levels was observed 1 month after treatment. At the 1.5-GBq/m2 dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m2, no grade 4 hematological toxicity was seen, but WBC and platelet counts of two of the three patients did not recover completely. One patient had a complete remission lasting 4 months. Four patients had a partial remission, lasting 3, 3, 6, and 14 months, respectively. Four patients had stable disease for 3, 3, 7, and 9 months, respectively. Conclusions: 186Re-epratuzumab at a dose of 2.0 GBq/m2 is well tolerated without major toxicity. A single dose of 186Re-epratuzumab led to objective responses in 5 of 15 treated patients.

Original languageEnglish
JournalClinical Cancer Research
Volume9
Issue number10 II
Publication statusPublished - 1 Oct 2003

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