Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma.

PURPOSE: Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL. PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m(2) weekly for 4 weeks) or time to progression (TTP) of < or = 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m(2) intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients. RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors > or = 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier-estimated TTP was 6.8 months (range, 1.1 to > or = 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively. CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma.

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 ((131)I), tositumomab, and yttrium 90 ((90)Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise.

Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I, single-dose, dose-escalating clinical trial.

BACKGROUND: CD23, a cell-surface molecule, is involved in a variety of pathways likely to influence IgE production and inflammation in allergic disorders, such as allergic rhinitis and allergic asthma. OBJECTIVE: This study investigated the safety, clinical activity, and pharmacokinetic profile of IDEC-152, an IgG1 anti-CD23 antibody, in patients with mild-to-moderate persistent allergic asthma. METHODS: This single-dose, dose-escalating, placebo-controlled study involved 30 patients. Cohorts of 3 to 6 patients received single intravenous infusions of either placebo or IDEC-152 (0.05, 0.25, 1.0, 4.0, 10.0, or 15.0 mg/kg) on study day 1. Safety, clinical activity, and pharmacokinetics were assessed for 12 weeks after treatment. RESULTS: IDEC-152 was well tolerated. Adverse events (AEs) were mild, no grade 4 or serious AEs were reported, and no relationships were apparent between the dose of IDEC-152 and the frequency, severity, or type of event. The most common AEs in the IDEC-152 group included ecchymosis at the injection site, sinusitis, headache, arthralgia, cold syndrome, infection, throat irritation, and dysmenorrhea. Commonly reported AEs in the placebo group included headache, abdominal pain, and infection. Sustained and dose-dependent decreases in mean IgE concentrations were noted. The mean maximum concentration and area under the curve of IDEC-152 were proportional to the dose administered for the dose range 4.0 to 15.0 mg/kg. The serum half-life of the IDEC-152 antibody increased from 2 to 10 days with increasing doses. After single-dose administration of IDEC-152, no dose-dependent change in FEV(1) was observed, and most changes in peak expiratory flow rate were within 10% of baseline values. CONCLUSION: These data suggest that IDEC-152 is safe and has the potential for clinical activity in allergic asthma.

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma.

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 (131I), tositumomab, and yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise. Semin Oncol 29 (suppl 2):87-92. Copyright © 2002 by W.B. Saunders Company.