Zevalin highly effective in first-line treatment of low-grade follicular lymphoma

Dec 6 2004

Results from a clinical trial presented at the American Society of Hematology 46th Annual Meeting and Exposition (ASH) demonstrated that Zevalin (ibritumomab tiuxetan), administered as a first-line therapy, induced a 100 percent response rate in a small population of patients with low-grate follicular lymphoma (FL).

"These data demonstrate Zevalin's effectiveness in the first-line treatment of previously untreated low grade follicular lymphoma patients," said John William Sweetenham, M.D., Professor of Medicine, University of Arizona Cancer Center, research conducted at the University of Colorado Health Sciences Center. "These results are exciting and further follow-up is needed to determine the long-term efficacy of combining frontline radioimmunotherapy with antibody-based maintenance."

Eight of the 10 patients treated with Zevalin were evaluated for treatment response. Of the eight patients, five (62 percent) had complete responses and three (38 percent) had partial responses to Zevalin induction therapy. Toxicities were manageable and primarily hematologic with grade three cytopenia occurring in 38 percent (3/8) of patients.

Patients were eligible for treatment if they presented with histologically confirmed, previously untreated low-grade FL. Additional eligibility criteria included stage III or IV disease and a need for therapeutic intervention because of constitutional symptoms, evidence of disease progression, or organ dysfunction directly attributable to NHL. Patients were excluded if there was evidence of histologic transformation to aggressive disease. The median age of patients was 58 years (range, 40 - 82) and 50 percent (5/10) of patients had stage IV disease. Delivered doses of 90Y ibritumomab tiuxetan ranged from 21-32 mCi.

On day one, patients received an initial infusion of rituximab (250 mg/m2) followed by an imaging dose of Indium 111 (111In) ibritumomab tiuxetan (5 mCi). One week later, a second infusion of rituximab (250 mg/m2) was given, proceeded by an injection of 90Y ibritumomab tiuxetan (0.3 or 0.4 mCi/kg, depending upon platelet count). Rituximab maintenance therapy (375 mg/m2 x 4) was scheduled at six-month intervals over two years. Endpoints included clinical response rates using standard International Workshop Response Criteria (IWRC) and toxicity.

Non-Hodgkin's lymphoma (NHL) is a type of malignant disease that occurs within the lymphatic system. It originates from lymphocytes, a type of white blood cells, which can be divided into two main types, B lymphocytes and T lymphocytes (also called B-cells or T-cells). In adults, approximately 85 percent of NHL cases are of B-cell origin.

The overall prevalence of NHL in the European Union is about 230,000 with an annual incidence of about 70,000. This incidence is currently increasing in Europe by four percent per year.

Non-Hodgkin's lymphomas can be divided clinically into two general categories: indolent lymphomas, which tend to grow relatively slowly, and aggressive lymphomas, which grow more rapidly. Indolent lymphomas include follicular NHL and were formerly commonly classified as "low-grade." Patients with indolent lymphomas often live for 10 years or more. Typically, the disease advances or transforms over time and because indolent lymphomas are usually not curable, these patients need new treatment alternatives. Indolent NHL represents around 45-50 percent of all NHL. The median age at diagnosis is 55-60 years.

NHL is slightly more common in men than women. Some risk factors include pre-existing infection (particularly HIV, Epstein-Barr virus and T-lymphotropic virus type 1), exposure to certain chemicals, previous organ transplant and family history of the disease.

Zevalin is the first commercially available radioimmunotherapy to treat forms of NHL. It combines the targeting power of an anti-CD20 monoclonal antibody with the radioisotope yttrium-90. The attachment of radiolabeled antibody to the NHL cells permits the radiation to penetrate the tumor from several angles and creates a potent cancer-cell destroying crossfire effect. Zevalin was approved by the United States Food and Drug Administration for use in the treatment of relapsed or refractory low-grade follicular or transformed NHL in February 2002. Schering AG, Germany received European Union approval for Zevalin for the treatment of adult patients with rituximab relapsed or refractory CD20-positive follicular B-cell non-Hodgkin's lymphoma (NHL) in January 2004.

jsweetenham @ azcc.arizona.edu