Iodine-131 tositumomab (Bexxar) is a new radioimmunotherapy in development for the treatment of patients with low-grade or transformed low-grade non-Hodgkins lymphoma. The data from five phase I-III studies, which enrolled patients with low-grade NHL or transformed low-grade NHL, were analyzed.
This analysis focuses on 179 patients with follicular small cleaved cell (FSCL) or follicular mixed cell with > 50% small cleaved cell (FML) histology at the time of treatment with tositumomab. Patients had received a median of 2 (range, 0 to 13) prior chemotherapy regimens, and 64 (49%) of 124 patients had failed to respond to their last chemotherapy regimen. The median duration of response to the last chemotherapy regimen was 6 months. Baseline patient characteristics were: median age, 52 years; 107 patients were male; median time from diagnosis to entry was 29 months; 38% of patients had elevated lactic dehydrogenase (LDH); 58% of patients had a positive baseline bone marrow biopsy (< 25% lymphoma).
Patients generally received a single dosimetric dose (450 mg of tositumomab intravenously [IV] followed by 35 mg of tositumomab radiolabeled with 5 mCi of iodine-131 over ½ hour) and then had three whole-body counts obtained over the next 7 days. The whole-body counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose (65 cGy for platelet counts of 100,000 to 149,999 cells/mm³ and 75 cGy for platelet counts ³ 150,000 cells/mm³). A single therapeutic dose (450 mg of tositumomab antibody IV followed by 35 mg of tositumomab containing an appropriate activity [mCi] of iodine-131 to deliver the specified total-body dose [cGy] over ½ hour) was administered 7 to 14 days after the dosimetric dose.
An overall response (complete and partial) was observed in 145 (81%) patients, and 69 (39%) patients had a complete response (CR). The median duration of response was 11 months (95% confidence interval [CI], 9 to 16 months), and median time to progression (TTP) for responders was 13 months (95% CI, 11 to 19 months). The median duration of CR was 57 months (95% CI, 31 months to not reached). Overall response by histology was: FSCL, 91 (83%) of 110 patients (38% CRs); and FML, 54 (78%) of 69 patients (39% CRs).
The principal toxicity was hematologic: absolute neutrophil count (ANC) was < 500 cells/mm³ in 17% of patients, and platelet count was < 10,000 cells/mm³in 3%. The hematologic nadir typically occurred at week 5 to 6, with recovery by week 8 to 9. Transient, mild to moderate nonhematologic toxicity occurred, with the most frequent events being fatigue (39%), fever (37%), and nausea (36%). Human antimurine antibodies developed in 12% of previously treated patients. Median survival from study entry was 74 months (95% CI, 36 months to not reached).
CONCLUSIONS: These results demonstrate that tositumomab is a safe and effective therapy for the treatment of patients with follicular NHL.