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


METHODS
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.


RESULTS
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.


CONCLUSIONS
(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.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D015815:Cell Adhesion Molecules; D005260:Female; D006801:Humans; D037102:Lectins / Q000096:biosynthesis; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use*; D011874:Radiometry; D012211:Rhenium / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2; D013667:Technetium / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D011868:Radioisotopes; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab; D012211:Rhenium; D013667:Technetium