Impact of Course of Therapy on Response Rate and Duration with the Bexxar® Therapeutic Regimen (Tositumomab and Iodine I 131 Tositumomab) and with Chemotherapy.

Low grade NHL with or without transformation is characterized by recurrence. Initial response rates with chemotx are high, but all patients ultimately relapse, and the response rates and durations of response typically decline with each subsequent course of chemotx. In the pivotal trial of Bexxar (JCO 19:3918 2001) there were significantly more patients with longer durations of response than after their last qualifying chemotx. The aim of the current retrospective study was to evaluate the efficacy of Bexxar and prior chemotx by course of treatment in a larger group of patients. Response rates (RR) and duration of response data were available from the treatment histories of the 230 patients from five clinical studies. Demographics: median age, 56 years; age > 60, 34%; median number of prior regimens, 3 (range 1–13); bone marrow involvement, 48%; bulky disease, 32%; transformed histology 28%; IPI score ≥ 2, 81%; and refractory to their preceding regimen, 80%. The patient-specific dosing regimen for Bexxar was previously described (JCO 19:3918). RR and durations for chemotx used as the 2nd, 3rd, 4th, 5th, 6th and >6th treatment were compared to Bexxar for the same numerical treatment. At each successive treatment course, there was a consistently higher RR and duration of response after Bexxar than after chemotx (Table). The actual differences in RR may be greater, as the data for Bexxar are based on responses observed on at least 2 evaluations >4 weeks apart, as assessed by an independent, blinded Masked Independent Randomized Radiology and Oncology (MIRROR) panel. The reported RR for chemotx are based on Investigator-assessed unconfirmed responses. Of note, the % responding pts in continuous response at ≥ five year after receiving Bexxar for the 2nd, 3rd, 4th, 5th, 6th and >6th relapse were 41%, 21%, 25%, 35%, 36 and 9%, respectively. While RR decreased with number of prior therapies, the durations of response and percent in continuous response after Bexxar were substantial and consistent across the range of the number of prior therapies.