Bexxar Approved for Relapsed/Refractory NHL

ROCKVILLE, Maryland—Bex-xar (tositumomab and iodine I-131 tositumomab) has received FDA approval for the treatment of patients with CD20-positive follicular non-Hodgkin’s lymphoma (NHL), with and without transformation, whose disease is refractory to rituximab (Rituxan) and has relapsed following chemotherapy. Bexxar will be co-marketed in the United States by Corixa Corporation, Seattle, and GlaxoSmith-Kline, Philadelphia.

Bexxar is a dual-action therapy that pairs the tumor-targeting ability of a cytotoxic monoclonal antibody (tositumo-mab) and the therapeutic potential of radiation (iodine-131) with patient-specific dosing.

The efficacy of the Bexxar therapeutic regimen was shown in a multicenter, single-arm study of 40 patients with follicular NHL whose disease had relapsed following rituximab or had not responded to rituximab. The results of this study were supported by demonstration of durable objective response in four other single-arm studies, enrolling 190 patients with rituximab-naïve, follicular NHL with or without transformation who had relapsed following chemotherapy or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47% to 64% (median duration, 12 to 18 months), Corixa and GlaxoSmith-Kline said in a press release.

Study results for Bexxar in patients with a durable response were recently reported at the 50th Annual Meeting of the Society of Nuclear Medicine (SNM), held in New Orleans. An analysis of data from the five clinical trials showed long-term durable remissions in 30% of patients with relapsed and refractory low-grade NHL. The results were seen after just a single treatment, with some remissions lasting up to 8 years, said Richard Wahl, MD, chairman of nuclear medicine, Johns Hopkins Medical Institutes.

The analysis included 250 patients who participated in the five clinical trials of NHL patients with relapsed or refractory disease. Of these patients, 76 (30%) met the definition for durable response, ie, an objective response lasting 12 months or longer by independent, blinded assessment. The median follow-up for these patients was 44.6 months, although some patients were treated as long ago as 8 years. Almost all of the durable responders received the 75 cGy prescribed dose of Bexxar (some received 65 cGy).

For the 76 durable responders, the rate of complete response was 76%, and median time to progression was 58.4 months. "These results were based on a single therapeutic administration of Bexxar, and we see response durations of 5 years. The longest response duration we’ve seen has been more than 8 years," Dr. Wahl said.

Most of the responders had received three prior chemotherapy regimens, and one third had received more than four; 38% had demonstrated no response to their last treatment. Considering the challenging patient population, and the tendency of NHL to relapse ever more frequently and with shorter response durations with successive therapies, "these findings are quite unexpected and exciting," Dr. Wahl said.

Using 10 prognostic factors, the investigators established that 80% of durable responders had at least three poor-prognostic features and 30% had five or more. The beneficial effects of long-term responses, therefore, did not result from a selection of better-prognosis patients, he pointed out.

Patients were less likely to achieve a durable response if they had a lack of response to their last chemotherapy, elevated lactate dehydrogenase (LDH), bulky disease, and modified International Prognostic Index (IPI) score of 3 or higher. Nonfollicular histology was also predictive of a less favorable response, indicating that the underlying substrate is important, he said.

Rituximab-Refractory Disease

In a separate retrospective analysis presented at SNM, 35 evaluable patients with rituximab-refractory disease had a 63% response rate to Bexxar, including complete responses in 29%, according to lead investigator Donald Podoloff, MD, of Texas Medical Center, Houston. The median duration of response was 25 months. In complete responders, median duration has not yet been reached at 28 months. With a follow-up of 40 months, eight patients (23%) remain in complete remission, Dr. Podoloff said.

Patients With Thrombocytopenia

Also presented at the SNM meeting were results showing that patients with mild thrombocytopenia can be safely and effectively treated with Bexxar using an attenuated 65 cGy total body dose. Stanley J. Goldsmith, MD, director of nuclear medicine, New York Presbyterian Hospital, presented the results.

The study evaluated this reduced dose in 190 patients with mild thrombocytopenia at baseline (platelet counts 100,000 to 149,999/µL), constituting 22% of the total 870 patients in the Bexxar clinical trials and an expanded access program. While about 50% of patients receiving Bexxar at 65 cGy had hematologic toxicity, the rate of serious infections was only 3.7%, and bleeding occurred in only 1.6%. Supportive care was required in 32% of patients. Importantly, the attenuated dose was associated with an overall response rate of 48% and a complete response rate of 25%; therefore, efficacy was not compromised. The low incidence of clinical consequences of the hematologic toxicity and the good response rates are similar to what is observed in patients with normal platelet counts receiving the 75-cGy dose.