Response to Tositumomab and Iodine ¹³¹I-Tositumomab (BEXXAR) Based on International Prognostic Index (IPI) Score.

Purpose: The therapeutic efficacy of Bexaar (tositumomab and131I tositumomab) in the treatment of follicular lymphoma patients who have relapsed or had refractory disease after rituximab has been demonstrated. A retrospective review has reported durable complete responses in patients who were both rituximab refractory and naive.¹ Results of an expanded access program reported a 59% overall response rate with a median duration of 15 months in patients with relapsed or refractory NHL.² We report results on 33 patients treated in the expanded access program and have attempted to identify patient characteristics predictive of response or outcome.

Methods: From April 1999 to November 2001, 33 patients with refractory NHL were enrolled in an IRB-approved expanded access trial at Tufts New England Medical Center. Patients were dosed with 450 mg of tositumomab and a total body exposure of 75cGy with ¹³¹I-tositumomab.

Results: Of 33 treated patients, 24 had follicular lymphoma, 6 had transformed to diffuse large cell lymphoma, and 3 had small lymphocytic lymphoma. Median prior therapies was 2 (range 1–6), with 18 rituximab refractory and 15 rituximab naïve. Of 33 evaluable patients, the overall response rate was 67%, with 59% (13/22) of responders achieving CR. Median progression free survival (PFS) of the responders was 19 months, compared to a median PFS of 4 months with their last therapy. Median overall survival was 44 months in the 22 responders compared to 23 months in non-responders (p=.002). Among all patients, 28 of 33 eventually developed progressive disease, and 17 deaths had occurred during this study period. Median time to ANC nadir was 41 days and PLT nadir occurred at a median of 34 days. Two patients developed AML/MDS, and no patient required long term treatment for thyroid dysfunction. When prognostic factors were considered, 15 patients had an International Prognostic Index (IPI) score of 4–5. The median survival in this group was 24 months, while patients with Intermediate risk IPI scores of 2–3 (18 pts) had not yet reached median survival at 42+ months. Duration of response was 12 months in the high-risk IPI group compared to 42 months in the intermediate-risk group (p=.0017). Prior rituximab was also an independent predictor of outcome, with a median response duration of 12 months in rituximab exposed vs 38 months in rituximab naïve patients (p=.03), although there was not a statistically significant difference in response rates between the two groups. Because or number of transformed patients was small, it was impossible to correlate response based on histology.

Conclusions: We report an overall response rate of 67% with a response duration of 19 months in responders. Median overall survival for responders was in excess of 44 months. Response duration was higher for patients with low -intermediate IPI scores and in rituximab naïve patients. A response duration of 12 months in the high IPI group in this retrospective analysis suggests that Bexaar therapy may be associated with an improved outcome compared to other therapies. Further prospective studies stratifying patients based on IPI score are underway.