Pivotal study of iodine I 131 Tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas

Purpose : To evaluate the efficacy and safety of tositumomab and iodine I 1 31 tositumomab (Bexxar, Corixa Corp, Seattle, WA, and GlaxoSmithKline, Phil adelphia, PA) in patients with chemotherapy-refractory low-grade or transfo rmed low-grade non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last qualifying chemotherapy (LQC) regimens. Patients and Methods: Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single co urse of iodine I 131 tositumomab. Results: Patients had received a median of four prior chemotherapy regimens . A partial or complete response (CR) was observed in 39 patients (65%) aft er iodine I 131 tositumomab, compared with 17 patients (28%) after their LQ C (P < .001). The median duration of response (MDR) was 6.5 months after io dine I 131 tositumomab, compared with 3.4 months after the LQC (P < .001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after io dine I 131 tositumomab (P < .001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after io dine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days diff erence) had a longer duration of response after iodine I 131 tositumomab (P < .001). Only one patient was hospitalized for neutropenic fever. Five pat ients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four p atients in follow-up. Conclusion: A single course of iodine I 131 tositumomab was significantly m ore efficacious than the LQC received by extensively pretreated patients wi th chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile. (C) 2001 by American Society of Clinical Onc ology.