FEASIBILITY AND PHARMACOKINETIC STUDY OF A CHIMERIC ANTI-CD20 MONOCLONAL-ANTIBODY (IDEC-C2B8, RITUXIMAB) IN RELAPSED B-CELL LYMPHOMA

Background: In clinical trials in the USA, IDEC-C2B8 (a mouse-human ch imeric anti-CD20 monoclonal antibody) has demonstrated high response r ates with only mild toxic effects in relapsed B-cell lymphoma at a dos e of four weekly 375 mg/m(2) infusions. The aim of the present trial w as 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 r elapsed CD20+ B-cell lymphoma received intravenous infusions of IDEC-C 2B8 once a week for four weeks. A total of 12 patients (four at 250 mg /m2 and eight at 375 mg/m(2)) were enrolled. Results. All 11 eligible patients treated with either dose level tolerated IDEC-C2B8 well. Comm only observed adverse drug reactions were grades 1 or 2 non-hematologi c toxicities during the infusion, consisting mostly of flu-like sympto ms and skin reactions. All of the observed hematologic toxicities were of grade 3 or less, and transient. A rapid and sustained B-cell decre ase in peripheral blood was observed, but no infectious episodes were encountered. Human anti-mouse and anti-chimeric antibodies were not de tected. Of the 11 eligible patients (eight with follicular, two with d iffuse large-cell and one with mantle cell lymphoma), two showed a com plete response and five showed a partial response, and all of the seve n responders had lymphoma with follicular histology. A pharmacokinetic analysis showed that the elimination half-life (T1/2) of IDEC-C2B8 wa s 445 +/- 361 hours, and that the serum antibody levels increased in p arallel with the course of infusions, and in most patients was still m easurable at three months. Conclusions. The dose of four weekly 375 mg /m(2) infusions of IDEC-C2B8 is safe and effective in Japanese patient s with relapsed B-cell lymphoma. Further studies evaluating IDEC-C2B8 are warranted.