Feasibility and Pharmacokinetic Study of a Chimeric Anti-CD20 Monoclonal Antibody (IDEC-C2B8, Rituximab) in Relapsed B-cell Lymphoma. The IDEC-C2B8 Study Group

Background: In clinical trials in the USA, IDEC-C2B8 (a mouse-human chimeric anti-CD20 monoclonal antibody) has demonstrated high response rates with only mild toxic effects in relapsed B-cell lymphoma at a dose of four weekly 375 mg/m2 infusions. The aim of the present trial was to determine whether or not this dose is practically applicable to Japanese patients with relapsed B-cell lymphoma with respect to safety, pharmacokinetics and efficacy.

Patients And Methods: Patients with relapsed CD20+ B-cell lymphoma received intravenous infusions of IDEC-C2B8 once a week for four weeks. A total of 12 patients (four at 250 mg/m2 and eight at 375 mg/m2) were enrolled.

Results: All 11 eligible patients treated with either dose level tolerated IDEC-C2B8 well. Commonly observed adverse drug reactions were grades 1 or 2 non-hematologic toxicities during the infusion, consisting mostly of flu-like symptoms and skin reactions. All of the observed hematologic toxicities were of grade 3 or less, and transient. A rapid and sustained B-cell decrease in peripheral blood was observed, but no infectious episodes were encountered. Human anti-mouse and anti-chimeric antibodies were not detected. Of the 11 eligible patients (eight with follicular, two with diffuse large-cell and one with mantle cell lymphoma), two showed a complete response and five showed a partial response, and all of the seven responders had lymphoma with follicular histology. A pharmacokinetic analysis showed that the elimination half-life (T1/2) of IDEC-C2B8 was 445 +/- 361 hours, and that the serum antibody levels increased in parallel with the course of infusions, and in most patients was still measurable at three months.

Conclusions: The dose of four weekly 375 mg/m2 infusions of IDEC-C2B8 is safe and effective in Japanese patients with relapsed B-cell lymphoma. Further studies evaluating IDEC-C2B8 are warranted.