IDEC-C2B8 (RITUXIMAB) ANTI-CD20 MONOCLONAL-ANTIBODY THERAPY IN PATIENTS WITH RELAPSED LOW-GRADE NON-HODGKINS-LYMPHOMA

IDEC-C2B8 is a chimeric monoclonal antibody (MoAb) directed against th e B-cell-specific antigen CD20 expressed on non-Hodgkin's lymphomas (N HL). The MoAb mediates complement and antibody-dependent cell-mediated cytotoxicity and has direct antiproliferative effects against maligna nt B-cell lines in vitro. Phase I trials of single doses up to 500 mg/ m(2) and 4 weekly doses of 375 mg/m(2) showed clinical responses with no dose-limiting toxicity. We conducted a phase II, multicenter study evaluating four weekly infusions of 375 mg/m(2) IDEC-C2B8 in patients with relapsed low-grade or follicular NHL (Working Formulation groups A-D). Patients were monitored for adverse events, antibody pharmacokin etics, and clinical response, Thirty-seven patients with a median age of 58 years (range, 29 to 81 years) were treated, All patients had rel apsed after chemotherapy (median of 2 prior regimens) and 54% had fail ed aggressive chemotherapy. Infusional side effects (grade 1-2) consis ting of mild fever, chills, respiratory symptoms, and occasionally hyp otension were observed mostly with the initial antibody infusion and w ere rare with subsequent doses. Peripheral blood B-cell depletion occu rred rapidly, with recovery beginning 6 months posttreatment. There we re no significant changes in mean IgG levels and infections were not i ncreased over what would be expected in this population. Clinical remi ssions were observed in 17 patients (3 complete remissions and 14 part ial remissions), yielding an intent to treat response rate of 46%. The onset of these tumor responses was as soon as 1 month posttreatment a nd reached a maximum by 4 months posttreatment. In the 17 responders, the median time to progression was 10.2 months (5 patients exceeding 2 0 months). Likelihood of tumor response was associated with a follicul ar histology, with the ability to sustain a high serum level of antibo dy after the first infusion, and with a longer duration of remission t o prior chemotherapy, One patient developed a detectable but not quant ifiable immune response to the antibody that had no clinical significa nce. IDEC-C2B8 in a dose of 375 mg/m(2) weekly for 4 weeks has antitum or activity in patients with relapsed low-grade or follicular NHL. Res ults with this brief, outpatient treatment compare favorably with resu lts with standard chemotherapy, and IDEC-C2B8 has a better safety prof ile. Further studies evaluating IDEC-C2B8 in other types of lymphoma e ither alone or combined with chemotherapy are warranted. (C) 1997 by T he American Society of Hematology.