Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma

Iodine-131 tositumomab (Bexxar) is a radiolabeled murine IgG2a monoclonal antibody directed against the CD20 antigen on B-cells. Sixty patients were enrolled at eight sites in this phase III study designed to compare efficacy outcomes between the patients’ last chemotherapy regimen and iodine-131 tositumomab. Thirty-six (60%) patients had low-grade non-Hodgkin’s lymphoma, 23 (38%) had transformed low-grade NHL, and 1 (2%) had mantle cell lymphoma. Patients had to have received ³ 2 different chemotherapy regimens and had to have not responded to or progressed within 6 months of their last chemotherapy regimen.

Baseline patient characteristics were: median age of > 60 years, male (63%), median time from diagnosis (54 months), elevated lactic dehydrogenase (44%), lymph node ³ 5 cm (65%), median number of prior chemotherapies (four).

Patients received saturated solution of potassium iodide (SSKI) or Lugol’s solution beginning ³ 24 hours before the dosimetric dose and continuing for 14 days after the therapeutic dose. Patients received a single dosimetric dose (450 mg of antibody IV over 1 hour, followed by 35 mg of antibody radiolabeled with 5 mCi of iodine-131 over ½ hour) and then had three whole-body gamma camera counts obtained over the next 7 days.

The gamma camera counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose (65 cGy to the whole body for platelets 100,001-149,999 cells/mm3 and 75 cGy for platelets ³ 150,000 cells/mm3). The single therapeutic dose (450 mg of unlabeled antibody IV over 1 hour, followed by 35 mg of radiolabeled antibody over ½ hour) was administered 7-14 days after the dosimetric dose.

An investigator-assessed response was observed in 17 (28%) of 60 patients following their last chemotherapy regimen, compared to 39 (65%) of 60 patients following iodine-131 tositumomab (P < .0001; McNemar’s test). A complete response was observed in 2 (3%) patients following their last chemotherapy regimen, compared with 10 (17%) patients following iodine-131 tositumomab (P = .01; McNemar’s test). Of the 41 patients having nonequivalent durations of response (ie, durations of response > 30 days different), 9 had a longer duration of response following their last chemotherapy regimen and 32 had a longer duration of response following iodine-131 tositumomab (P = .0001; McNemar’s test). These response outcomes were reviewed by a masked independent randomized radiology and oncology review (MIRROR) panel and were confirmed.

The principal toxicity was hematologic; absolute neutrophil count (ANC) < 100 was 2%; platelets < 10,000 cells/mm³, 2%. The nadir typically occurred at week 5-6 with recovery by week 8-9. Transient, mild to moderate nonhematologic toxicity occurred, with the most frequent events being fatigue, fever, and nausea. Four (7%) patients developed antimurine antibodies.

CONCLUSION: These results confirm earlier data and indicate that iodine-131 tositumomab is a safe and effective new agent for the treatment of low-grade or transformed low-grade NHL.

Click here for Dr. Bruce Cheson’s commentary on this abstract.