Zevalin boosts PFS in advanced follicular NHL patients

ATLANTA-Consolidation therapy using Zevalin (90yttrium-ibritumomab tiuxetan) following first remission significantly extends progression-free survival in patients with advanced-stage follicular non-Hodgkin's lymphoma, Anton Hagenbeek, MD, PhD, said at the 49th Annual Meeting of the American Society of Hematology (abstract 643).

Dr. Hagenbeek, of the Department of Hematology, University of Utrecht, The Netherlands, noted that remission of follicular lymphoma can be achieved with chemotherapy, but relapsed/refractory disease is common, and new treatment options are needed. Lymphoma cells are known to be highly sensitive to the cytotoxic effects of radiation.

This international, randomized phase III trial, known as the First-line Indolent Trial (FIT), tested whether Zevalin consolidation therapy could extend progression-free survival (PFS) in advanced-stage NHL patients with minimal residual disease following response to first-line chemotherapy.

Major inclusion criteria included CD20-positive grade 1 or 2 follicular lymphoma, stage III or IV disease at diagnosis, less than 25% bone marrow involvement, and complete or unconfirmed complete response (CR/CRu) or partial response (PR) after first-line chemotherapy. A total of 414 patients were enrolled at 77 centers between August 2001 and January 2005. Patients responding to induction therapy were randomized to consolidation treatment or no further treatment. Consolidation consisted of 250 mg/m² rituximab (Rituxan) on days –7 and 0 plus, on day 0, Zevalin 0.4 mCi/kg (maximal dose 32 mCi).

Study results

At median follow-up of 3.5 years, treatment with Zevalin increased median PFS by 2 years, from 13.5 months to 37 months (P < .001, HR 0.465). For patients who experienced a PR, median PFS (based on time from randomization) increased from 6.3 months to 29.7 months with consolidation therapy (P < .0001, HR 0.304), and for those who attained a CR, median PFS increased from 29.2 months to 54.6 months (P = .01, HR 0.609).

Consolidation therapy with Zevalin resulted in high conversion rates from PR to CR (77%), independent of first-line therapy administered, Dr. Hagenbeek said. This conversion rate was superior to that seen in historic studies employing other therapies such as myeloablative regimens (range, 38% to 69%).

Overall, 87% of patients achieved CR: 76% CR and 11% CRu. Molecular studies revealed a high (97%) molecular remission rate in blood.

Quality-of-life analysis demonstrated no significant differences with Zevalin therapy relative to control. No differences were noted in the activity of Zevalin across FLIPI subtypes.

Zevalin was generally well tolerated. "The favorable toxicity profile was exactly as expected based on previous studies with Zevalin," Dr. Hagenbeek said. Grade 3-4 neutropenia occurred in 66% of Zevalin patients and grade 3-4 thrombocytopenia in 60%. To date, the number of deaths on study is equal (6 Zevalin, 5 control).

Patients will continue to be monitored to determine whether Zevalin also provides a benefit in overall survival.