Data regarding adverse events were primarily obtained in 230 patients with non-Hodgkin’s lymphoma enrolled in five clinical trials using the recommended dose and schedule. Patients had a median follow-up of 39 months and 79% of the patients were followed at least 12 months for survival and selected adverse events. Patients had a median of 3 prior chemotherapy regimens, a median age of 55 years, 60% male, 27% had transformation to a higher grade histology, 29% were intermediate grade and 2% high grade histology (IWF) and 68% had Ann Arbor stage IV disease. Patients enrolled in these studies were not permitted to have prior hematopoietic stem cell transplantation or irradiation to more than 25% of the red marrow. In the expanded access program, which included 765 patients, data regarding clinical serious adverse events and HAMA and TSH levels were used to supplement the characterization of delayed adverse events (see ADVERSE REACTIONS, Hypothyroidism, Secondary Leukemia and Myelodysplastic Syndrome, Immunogenicity).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Hematologic Events
Hematologic toxicity was the most frequently observed adverse event in clinical trials with the BEXXAR therapeutic regimen (Table 6). Sixty-three (27%) of 230 patients received one or more hematologic supportive care measures following the therapeutic dose: 12% received G-CSF; 7% received Epoetin alfa; 15% received platelet transfusions; and 16% received packed red blood cell transfusions. Twenty-eight (12%) patients experienced hemorrhagic events; the majority were mild to moderate.

Infectious Events
One hundred and four of the 230 (45%) patients experienced one or more adverse events possibly related to infection. The majority were viral (e.g., rhinitis, pharyngitis, flu symptoms, or herpes) or other minor infections. Twenty of 230 (9%) patients experienced infections that were considered serious because the patient was hospitalized to manage the infection. Documented infections included pneumonia, bacteremia, septicemia, bronchitis, and skin infections.

Hypersensitivity Reactions
Fourteen patients (6%) experienced one or more of the following adverse events: allergic reaction, face edema, injection site hypersensitivity, anaphylactic reaction, laryngismus, and serum sickness. In the post-marketing setting, severe hypersensitivity reactions, including fatal anaphylaxis have been reported.

Gastrointestinal Toxicity
Eighty-seven patients (38%) experienced one or more gastrointestinal adverse events, including nausea, emesis, abdominal pain, and diarrhea. These events were temporally related to the infusion of the antibody. Nausea, vomiting, and abdominal pain were often reported within days of infusion, whereas diarrhea was generally reported days to weeks after infusion.

Infusional Toxicity
A constellation of symptoms, including fever, rigors or chills, sweating, hypotension, dyspnea, bronchospasm, and nausea, have been reported during or within 48 hours of infu