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-Hodgkins 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
Lugols 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
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;
McNemars 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;
McNemars 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; McNemars test).
These response outcomes were reviewed by a masked independent
randomized radiology and oncology review (MIRROR) panel and were
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.