Corixa and GlaxoSmithKline Announce Results of Two Studies of BEXXAR(R) Following Chemotherapy as First-Line Treatment of Non-Hodgkin's Lymphoma Presented At ASCO
Monday June 7, 7:01 am ET
NEW ORLEANS, June 7 /PRNewswire-FirstCall/ -- Therapy with two different standard chemotherapeutic regimens, each followed by a single treatment with the BEXXAR® therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab), produced complete responses in 80-83 percent of patients as initial treatment for advanced follicular B-cell non-Hodgkin's lymphoma, according to research presented at the 40th annual meeting of the American Society of Clinical Oncology (ASCO). In the first study, investigators reported that 72 percent of patients who received sequential therapy with fludarabine and BEXXAR and achieved a complete response remained disease free after a median follow-up of nearly four and a half years (ASCO Abstract 6518). In a second study, the chemotherapy regimen CVP followed by BEXXAR produced a complete response rate of 80 percent, with 77 percent of patients continuing in response after a median follow-up of 2.3 years (ASCO Abstract 6520).
"These data contribute to our growing picture of the utility of BEXXAR in the treatment of non-Hodgkin's lymphoma, particularly its ability to produce durable remissions in some patients with advanced disease," said John P. Leonard, M.D., Clinical Director, Center for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York.
The BEXXAR therapeutic regimen is indicated for the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma, with and without transformation, whose disease is refractory to the antibody treatment Rituximab and has relapsed following chemotherapy. The BEXXAR therapeutic regimen is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin's lymphoma. 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 or irradiation or chemotherapy, has not been evaluated.
Fludarabine/BEXXAR Sequential Therapy Produced Durable Remissions
Dr. Leonard reported long-term follow-up data on 35 patients who received three cycles of fludarabine followed by the BEXXAR therapeutic regimen between August 1998 and June 1999 for previously untreated, advanced, low-grade non- Hodgkin's lymphoma. At the time of enrollment, 97 percent of patients had stage III/IV disease.
Response to fludarabine was 89 percent (9 percent complete responses, 80 percent partial responses). After completion of fludarabine/BEXXAR, all subjects (100 percent) had a response, including 83 percent with a complete response and 17 percent with a partial response. With a median follow-up of 4.4 years, median progression-free survival has not been reached, and 72 percent of patients (25) who achieved a complete response remain in remission (range 1.3 to 5.0 years).
"We were pleased to observe that the complete responses achieved by a majority of patients following fludarabine/BEXXAR have persisted over time," said Dr. Leonard.
The principal adverse event associated with the sequential therapy was significant depression of blood counts, with grade 4 neutropenia, thrombocytopenia, and anemia noted in 34 percent, 29 percent and 3 percent of patients, respectively. Sixteen patients (46 percent) received growth factors or transfusions but there were no serious infections. Four patients (12 percent) developed elevated thyroid stimulating hormone (TSH) levels and two (6 percent) became positive for human anti-mouse antibody (HAMA). After a median follow-up of 4.4 years, none of the patients have developed secondary cancers, such as MDS or AML.
The Majority of Patients Achieved Complete Response to CVP/BEXXAR Therapy
Data were also reported from a Phase II, open-label, multicenter study in which 30 patients with previously untreated follicular non-Hodgkin's lymphoma received six cycles of CVP (cyclophosphamide, vincristine, and prednisone) followed by the BEXXAR therapeutic regimen. Enrolled patients ranged in age from 34 to 72 years (median 52 years). Ninety-seven percent had stage III or stage IV disease and half had a maximum tumor diameter of 5 cm or greater.
Following CVP therapy, 100 percent of patients had a response (50 percent complete response, 50 percent partial response). After completion of CVP/BEXXAR, the proportion of patients achieving a complete response increased from 50 percent to 80 percent. With a median follow-up of 2.3 years from initiation of therapy, the median progression-free survival has not been reached and 77 percent (23 patients) continue in response (range 0.6 to 3.4 years).
"CVP/BEXXAR appears to be a regimen with clinical activity for patients with previously untreated, advanced-stage, follicular non-Hodgkin's lymphoma and warrants further evaluation in larger trials," said Brian Link, M.D., Associate Professor of Medicine, University of Iowa Hospitals and Clinics. "This is one of several presentations at this meeting suggesting that the use of newer agents in regimens to treat follicular lymphoma can frequently result in long remissions without using an anthracycline. The significance of this will become a little clearer with longer follow-up."
The investigators reported that following BEXXAR, grade 4 neutropenia and thrombocytopenia occurred in 33 percent and 23 percent of patients, respectively. There were no serious infections and no cases of conversion to HAMA positivity were reported. One patient developed AML.
About the BEXXAR Therapeutic Regimen
BEXXAR pairs the targeting ability of a monoclonal antibody (Tositumomab) and the therapeutic potential of radiation (Iodine-131). Combined, these agents form a radiolabeled monoclonal antibody regimen that is able to bind to the target antigen CD20 found on B-cells, including normal cells and those that become cancerous in non-Hodgkin's lymphoma, thereby delivering the dose of radiation. BEXXAR, which is given in four visits over one to two weeks, is specifically dosed based on an individual's drug clearance rate, allowing the delivery of a pre-determined amount of radiation to each patient.
The BEXXAR therapeutic regimen has been studied for over 13 years. In a multi-center, single-arm, clinical trial in patients who had received an average of 4 prior chemotherapies and who had Rituximab-refractory disease (N=35), 63 percent (22 of 35) responded to BEXXAR. The median duration of response was 25 months. The results of this study were supported by demonstration of durable objective responses in four single-arm studies enrolling 190 patients evaluable for efficacy with Rituximab-naove, follicular non-Hodgkin's lymphoma with or without transformation, who had relapsed following or were refractory to chemotherapy. Determination of clinical benefit of the BEXXAR therapeutic regimen was based on evidence of durable responses without evidence of an effect on survival.
BEXXAR may not be for everyone. Patients who are pregnant or allergic to any components of the regimen should not receive BEXXAR. Treatment with BEXXAR resulted in very low blood counts in the majority of patients, which could be serious, for an extended period of time (about a month). Infections occurred in almost half the patients, bleeding in 1 of 8 patients, and treatment with supportive care in about 1 of 4 patients. Allergic reactions, including anaphylaxis, which may be severe, have occurred in patients receiving BEXXAR. Other less severe reactions during or following the infusion have included fever, chills, sweating, nausea, low blood pressure, shortness of breath and trouble breathing. Patients may also experience weakness, fever, nausea, increased cough, infection, pain, chills, rash, or headache. There is a risk of hypothyroidism following the administration of BEXXAR. Administration of BEXXAR resulted in the development of antibodies to the mouse antibody (called HAMA). Certain cancer therapies including BEXXAR have been associated with the development of a second type of blood cancer and solid tumors. Thirty-two cases (3.2 percent) of myelodysplastic syndrome (a type of pre-leukemia) and/or leukemia and 52 cases of secondary tumors were reported in 995 patients enrolled in BEXXAR studies. After being treated with BEXXAR, less than 5 percent of patients suffered hair loss or developed severe nausea, vomiting or mucositis (sores in mouth or gastrointestinal tract). Healthcare providers must be specifically trained to administer BEXXAR.
BEXXAR was developed by Corixa Corporation and is co-marketed in the United States by Corixa Corporation and GlaxoSmithKline. Additional information about the BEXXAR therapeutic regimen, including complete prescribing information, may be obtained by calling 1-877-4BEXXAR or visiting www.BEXXAR.com.
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Source: GlaxoSmithKline |
