anded access programs was 3% (20/765), with a median follow-up of 27 months and a median time to development of MDS of 31 months. The cumulative incidence of MDS/secondary leukemia in this patient population was 1.6% at 2 years and 6% at 5 years.
Secondary Malignancies
Of the 995 patients in clinical studies and the expanded access programs, there were 65 reports of second malignancies in 54 patients, excluding secondary leukemias. The most common included non-melanomatous skin cancers (26), colorectal cancer (7), head and neck cancer (6), breast cancer (5), lung cancer (4), bladder cancer (4), melanoma (3), and gastric cancer (2). Some of these events included recurrence of an earlier diagnosis of cancer.
Hypothyroidism
Of the 230 patients in the clinical studies, 203 patients did not have elevated TSH upon study entry. Of these, 137 patients had at least one post-treatment TSH value available and were not taking thyroid hormonal treatment upon study entry. With a median follow up period of 46 months, the incidence of hypothyroidism based on elevated TSH or initiation of thyroid replacement therapy in these patients was 18% with a median time to development of hypothyroidism of 16 months. The cumulative incidences of hypothyroidism at 2 and 5 years in these 137 patients were 11% and 19% respectively. New events have been observed up to 90 months post-treatment.
Of the 765 patients in the expanded access programs, 670 patients did not have elevated TSH upon study entry. Of these, 455 patients had at least one post-treatment TSH value available and were not taking thyroid hormonal treatment upon study entry. With a median follow up period of 33 months, the incidence of hypothyroidism based on elevated TSH or initiation of thyroid replacement therapy in these 455 patients was 13% with a median time to development of hypothyroidism of 15 months. The cumulative incidences of hypothyroidism at 2 and 5 years in these patients were 9% and 17%, respectively.
Immunogenicity
One percent (11/989) of the chemotherapy-relapsed or refractory patients included in the clinical studies or the expanded access program had a positive serology for HAMA prior to treatment and six patients had no baseline assessment for HAMA. Of the 230 patients in the clinical studies, 220 patients were seronegative for HAMA prior to treatment, and 219 had at least one post-treatment HAMA value obtained. With a median observation period of 6 months, a total of 23 patients (11%) became seropositive for HAMA post-treatment. The median time of HAMA development was 6 months. The cumulative incidences of HAMA seropositivity at 6 months, 12 months, and 18 months were 6%, 17% and 21% respectively.
Of the 765 patients in the expanded access programs, 758 patients were seronegative for HAMA prior to treatment, and 569 patients had at least one post-treatment HAMA value obtained. With a median observation period of 7 months, a total of 57 patients (10%) became seropositive for HAMA post-treatment. The median time of HAMA development was 5 months. The cumulative incidences of HAMA seropositivity at 6 months, 12 months, and 18 months were 7%, 12% and 13%, respectively.
In a study of 76 previously untreated patients with low-grade non-Hodgkin’s lymphoma who received the BEXXAR therapeutic regimen, the incidence of conversion to HAMA seropositivity was 70%, with a median time to development of HAMA of 27 days.
The data reflect the percentage of patients whose test results were considered pos
