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

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.