Radiolabeled Tositumomab for Transformed Low-Grade NHL

NEW ORLEANS—The arrival of new antibody-based radioimmunothera-pies may change the bleak prognosis for low-grade non-Hodgkin’s lymphoma (NHL) that transforms to a more aggressive histology.

In a retrospective analysis of patients with transformed low-grade NHL, Andrew D. Zelenetz, MD, PhD, chief of the Lymphoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, found that treatment with radiolabeled tositumomab (Bexxar) produced an overall response rate of 53%.

Response Duration

Median response duration from the time of treatment was 11 months overall and 20 months in patients with a complete response. Dr. Zelenetz presented these findings at the 41st annual meeting of the American Society of Hematology.

The data for the analysis were drawn from three phase I to III multicenter clinical trials plus two compassionate-use patients. There were 59 patients, but results for one patient were too early for analysis.

The majority of patients had diffuse B-cell lymphoma (see Table). Patients were initially diagnosed with low-grade disease (small cell lymphocytic, follicular small cleaved cell, or follicular mixed cell with more than 50% small cleaved cell). Transformation was demonstrated by biopsy evidence of a more aggressive histology at any time prior to study entry.

Patients had received a median of four prior chemotherapy regimens, and the median duration of response to the last previous chemotherapy was 4 months. Forty-eight percent of patients had not responded to chemotherapy. Chemotherapy had produced a complete response in 22% of patients, with a median duration of 6 months.

Patients received a single dosimetric dose of 450 mg of tositu-momab IV followed by 35 mg of tositumo-mab radiolabeled with 5 mCi of iodine 131. Whole body counts were used to calculate the required activity for delivering the desired therapeutic dose of 65 cGy for patients with platelet counts of 100,000 to 149,999 cells/mm³ and 75 cGy for patients with platelet counts over 150,000 cells/mm³.

Patients then received a single therapeutic dose of 450 mg of tositumomab IV followed by 35 mg of tositumomab containing the therapeutic dose of iodine 131.

Dr. Zelenetz reported that some type of response occurred in 31 of 58 patients (53%), including complete responses in 17 patients (29%).

When the data were analyzed excluding patients with follicular large-cell lymphoma, who are thought to have a better prognosis, the overall response rate was 46% (12 of 46 patients), and the median duration of response was 10 months. In this subset, the complete response rate was 22% (10 patients), with a median response duration of 20 months.

To determine whether patients with newly transformed disease would respond well, the researchers analyzed overall response according to time from disease transformation in 6-month increments. Response ranged from 42% to 62% but was not significantly different among cohorts and did not correlate with time since transformation.

“This was a surprising result,” Dr. Zelenetz said in an interview with ONI. “There was no significant difference in time of response to treatment based on time since transformation. This is clearly a very active therapy in patients who do poorly on other forms of treatment,” he commented.

The principal toxicity was hematologic: 19% of patients had an absolute neutrophil count of less than 500 cells/mm³, and 4% had platelet counts less than 10,000 cells/mm³. The nadir typically occurred at week 5 to 6, with recovery by week 8 to 9.

“These are difficult patients, but when tositumomab is approved for clinical use, we will have a new therapy that can help them,” Dr. Zelenetz said.