Phase II trial shows effective therapy for large B-cell lymphoma

Results from a phase II trial presented at the 9th International Congress on Malignant Lymphoma offer evidence that Zevalin (yttrium-90 ibritumomab tiuxetan) is effective as a second-line treatment for patients with diffuse large B-cell lymphoma (DLBCL) who are not suitable for stem cell transplantation.

'The results of this study demonstrate proof of principle that Zevalin can be an effective therapy for patients with diffuse large B-cell lymphoma,' said Dr Franck Morschhauser, senior consultant in Haematology, Hospital Claude Huriez, CHU in Lille, France. 'These data also suggest that Zevalin should be further evaluated in first-line treatment of diffuse large B-cell lymphoma.'

Zevalin induced high response rates in DLBCL patients who have relapsed or who are refractory to combination chemotherapy (i.e. CHOP or CHOP-like) with or without rituximab. Overall response rates (ORR) ranged from 20% to 58% in the study. The highest observed complete response rate was up to 45%. Durable responses were seen in all patient groups. Around 20% of the patients are still in response after at least one year of follow-up.

Patients who have relapsed or who are refractory following CHOP or R-CHOP (CHOP-rituximab) therapy generally have a poor prognosis, especially those who are not candidates for stem cell transplantation. These results suggest that Zevalin may be a treatment option for these patients.

About the Study

Researchers of this pan-European study conducted a prospective, single-arm, open-label, non-randomised, multi-centre Phase II trial to evaluate the efficacy and safety of yttrium-90 ibritumomab tiuxetan in elderly patients who have relapsed or who were refractory to first-line chemotherapy combinations such as CHOP or CHOP + rituximab and who were not eligible for stem cell transplantation. The trial comprised a total of 104 patients who were divided into two groups: those previously treated with chemotherapy alone (n=76), and those previously treated with chemotherapy and rituximab (n=28). All patients received a single dose of yttrium-90 ibritumomab tiuxetan. All of the 104 patients were evaluable for safety and 100 were evaluable for efficacy. The primary endpoint was overall response (ORR) assessed by using standard International Workshop Response Criteria (IWRC) at weeks 6, 12, and 24. Non-hematologic adverse events (AEs) were generally mild to moderate. Severe thrombocytopenia was the most significant side effect. Infections / fever were reported as serious adverse events (SAE) in 7.7% of patients during the study.

About NHL

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 cell, which can be divided into two main types, B lymphocytes and T lymphocytes (also called B-cells or T-cells). In adults, approximately 90 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 4%. Non-Hodgkin's lymphomas can be divided clinically into two general categories: indolent lymphomas, mainly typified as follicular lymphoma, which tend to grow relatively slowly, and aggressive lymphomas, mainly typified as diffuse large B-cell lymphoma (DLBCL), which grow more rapidly. DLBCL is the most common lymphoma subtype, accounting for 50% of all non-Hodgkin's lymphomas among elderly patients. The prognosis is poor for patients who have relapsed or who are refractory following CHOP or R-CHOP regimen. The prognosis is especially poor for those who are not candidates for stem cell transplantation. At present, there is no standard second-line treatment regimen for older patients in this situation.

About Zevalin

Zevalin (yttrium-90 ibritumomab tiuxetan) is the first commercially available radioimmunotherapy to treat forms of NHL. It combines the targeting ability of an anti-CD20 monoclonal antibody with the cytotoxic power of beta radiation emitted by the yttrium-90 isotope - a pure beta emitter. The attachment of radiolabeled antibody to NHL cells permits the radiation to penetrate the tumour from several angles and creates a potent lymphoma-/tumour-cell destroying crossfire effect. Zevalin was approved by the FDA for use in the treatment of relapsed or refractory low-grade follicular or transformed NHL in February 2002. In the European Union, Zevalin is approved for the treatment of adult patients with rituximab relapsed or refractory CD20-positive follicular B-cell non-Hodgkin's lymphoma (NHL) since January 2004.