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Non-Hodgkin's Lymphoma Patients Have High Response Rate With Tositumomab

SEATTLE & PHILADELPHIA--(BUSINESS WIRE)--Sept. 22, 2003--A novel therapeutic approach of BEXXAR(R) (Tositumomab and Iodine I 131 Tositumomab) following chemotherapy has been shown to produce a high rate of response in patients with advanced follicular non-Hodgkin's lymphoma (NHL), according to the results of a study published in the September 1, 2003 issue of Blood, the Journal of the American Society of Hematology. The Phase II clinical study assessed a two-part treatment consisting of CHOP chemotherapy (a combination-chemotherapy regimen) followed by the BEXXAR therapeutic regimen. This is the first fully published study of a combination treatment involving chemotherapy and radioimmunotherapy in the first-line treatment of follicular NHL. The treatment produced an overall response rate of 90 percent and a two-year overall survival rate of 97 percent.(1)

"The survival rates demonstrated in this study, and the significant time during which the disease did not progress, are impressive," said Southwest Oncology Group (SWOG) investigator and lead author Oliver W. Press, MD, member, Fred Hutchinson Cancer Research Center and professor of medicine at the University of Washington. "These clinical results are very positive compared to historical SWOG investigations of CHOP alone for follicular lymphoma."

SWOG is one of the largest cooperative groups funded by the National Cancer Institute (NCI) and has been conducting cancer clinical trials for the past 45 years. Its focus is on the treatment and prevention of adult cancers.

The study was conducted at 34 SWOG sites in the United States, many of them community-based hospitals. It was designed for sequential treatments of CHOP followed by BEXXAR due to concerns over potential bone marrow suppression if the two were given concurrently. BEXXAR was the radioimmunotherapy chosen for this study based on the substantial follow-up data available for BEXXAR and on the radioactive characteristics of BEXXAR for treating this type of cancer.

The study enrolled 90 eligible patients with previously untreated, advanced-stage disease. The combination of CHOP/BEXXAR produced an overall response rate of 90 percent, including a complete response rate (complete elimination of signs and symptoms of lymphoma) of 67 percent. The estimated 2-year progression-free survival and overall survival were 81 percent and 97 percent, respectively. Importantly, therapy with BEXXAR improved the overall best-response rate compared to CHOP alone. Among 47 patients who achieved less than a complete response following CHOP and for whom data were available on response after each stage of the regimen, 27 patients, or 57 percent, improved their remission status after receiving BEXXAR.

The treatment was well tolerated in the majority of patients. Ninety-six percent of eligible patients completed CHOP therapy as planned and 90 percent of eligible patients who completed CHOP also completed BEXXAR therapy. The main side effect was a suppression of blood cell production by the bone marrow, which can lead to the possibility of infections or bleeding and the need for blood transfusions. The bone marrow suppression was more pronounced during CHOP therapy than during administration of BEXXAR. After CHOP, 45 patients (52 percent) had Grade 3 or 4 neutropenia, one patient (1 percent) had Grade 3 thrombocytopenia, and three (3 percent) had Grade 3 anemia. After BEXXAR, 13 patients (16 percent) had Grade 3 or 4 neutropenia, 11 patients (13 percent) had Grade 3 or 4 thrombocytopenia, and two (2 percent) had Grade 4 anemia. Five patients developed Grade 3 or 4 cardiovascular toxicity after CHOP and one patient experienced a Grade 4 anaphylactoid reaction to the administration of BEXXAR. One case of myelodysplasia (MDS, a pre-leukemia condition) was reported 16 months after therapy and seven percent of patients received thyroid replacement therapy although none of the patients experienced symptomatic hypothyroidism.

"Although long-term follow up will be necessary to fully measure any potential impact from this treatment on the bone marrow in terms of cell damage or carcinogenic changes, our first impressions from the study results are that this regimen was generally well tolerated," said Dr. Press. "Most toxicities occurred during the CHOP segment of treatment and were reversible. Overall, we were pleased to observe manageable levels of toxicity, especially hematological toxicity, with this novel therapeutic approach of BEXXAR following CHOP."

The study protocol consisted of administering CHOP chemotherapy on 21-day intervals for six cycles. Patients were eligible for BEXXAR administration if their follicular non-Hodgkin's lymphoma showed at least a partial response four weeks to eight weeks after the completion of CHOP therapy, their blood cell counts were adequate, and the lymphoma occupied no more than 25 percent of the bone marrow. BEXXAR was given in a single, short course of treatment, individualized for each patient, consisting of two steps performed in four visits over seven days to 14 days. In the study, the regimen was administered in both academic and community-based hospital treatment settings.

Based on the encouraging results of this Phase II study, SWOG is currently conducting a Phase III randomized clinical study (S0016) comparing CHOP plus BEXXAR to CHOP plus the monoclonal antibody Rituximab in patients with advanced follicular NHL. S0016 is open to patients who are previously untreated for follicular NHL that expresses the CD20 antigen. For more information on this clinical study and study entry criteria, please call the SWOG Operations Office at 210-677-8808 or visit the NCI website at www.nci.nih.gov or the SWOG website at https://www.swog.org/.

About the BEXXAR Therapeutic Regimen
BEXXAR(R) (Tositumomab and Iodine I 131 Tositumomab) is approved for the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma (NHL), with and without transformation, whose disease is refractory to Rituximab and has relapsed following chemotherapy. The BEXXAR therapeutic regimen is not indicated for the initial treatment of patients with CD20 positive NHL. The BEXXAR therapeutic regimen is intended as a single course of treatment. The safety of multiple courses of the BEXXAR therapeutic regimen, or combination of this regimen with other forms of irradiation or chemotherapy, has not been evaluated. BEXXAR is co-marketed in the United States by Corixa Corporation (Nasdaq:CRXA) and GlaxoSmithKline (NYSE:GSK).

The principal dose limiting toxicity of BEXXAR in clinical trials was bone marrow suppression that could be prolonged and severe and required supportive care in approximately a quarter of the patients. Some patients also experienced weakness, nausea, fever, infection and cough, which were mild to moderate in severity. The BEXXAR therapeutic regimen was associated with a risk of hypothyroidism and human anti-murine antibody (HAMA) formation. Certain chemotherapy agents and ionizing radiation have been associated with the development of myelodysplasia (MDS), secondary leukemia and solid tumors. MDS, secondary leukemia and solid tumors have also been observed in patients receiving the BEXXAR therapeutic regimen. BEXXAR carries a warning about infusion-related reactions that may be induced by the administration of foreign proteins. Patients who are pregnant should not be treated with BEXXAR.

Please consult the complete Prescribing Information for more information on BEXXAR.

Healthcare professionals and people with non-Hodgkin's lymphoma may obtain more information about the BEXXAR therapeutic regimen by calling 1-877-4BEXXAR or visiting www.bexxar.com.

About Non-Hodgkin's Lymphoma
NHL is a form of cancer that affects the blood, bone marrow and lymphatic tissues. Non-Hodgkin's lymphoma currently is the sixth-leading cause of cancer-related deaths in the United States, is expected to claim the lives of 23,400 Americans this year, and has the second-fastest growing mortality rate. According to statistics from the National Cancer Institute (NCI), approximately 300,000 people are afflicted with NHL in the United States alone. Of that total, 25 percent to 40 percent have follicular NHL, making it the second most common type. Transformed NHL is an aggressive and difficult to treat form of follicular NHL with a particularly poor prognosis.

Source: Corixa Corporation, GlathoSmithKline

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