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

E. Postema, J. Raemaekers, W. Oyen, O. Boerman, C. Mandigers, D. Goldenberg, G. van Dongen and F. Corstens

Department of Nuclear Medicine, University Medical Center Nijmegen, 6500 HB Nijmegen, the Netherlands. e.postema@nucmed.umcn.nl
Sep, 2003

Abstract

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 (186)Re-epratuzumab in patients with NHL.Patients with relapsed or refractory CD22-positive NHL of diverse histopathology and prior treatments received (99m)Tc-labeled epratuzumab (anti-CD22 IgG1), followed by RIT with (186)Re-epratuzumab 1 week later. Dose escalation of RIT was started at 0.5 GBq/m(2). Three patients were entered per dose level. If no dose-limiting toxicity occurred, the dose was increased by 0.5 GBq/m(2); otherwise three additional patients were included on that dose level.A total of 18 patients received a diagnostic dose of (99m)Tc-epratuzumab. Fifteen patients were actually treated with (186)Re-epratuzumab at four different dose levels, 0.5, 1.0, 1.5, and 2.0 GBq/m(2). During or after infusion of (186)Re-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/m(2) dose level, one grade 4 hematological toxicity was observed. At the highest dose level of 2 GBq/m(2), 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.(186)Re-epratuzumab at a dose of 2.0 GBq/m(2) is well tolerated without major toxicity. A single dose of (186)Re-epratuzumab led to objective responses in 5 of 15 treated patients.