The First-line Indolent Trial (FIT) demonstrated that ibritumomab tiuxetan (Zevalin) improved the median progression-free survival period among patients with CD-2-positive follicular non-Hodgkin's lymphoma when used as first-line consolidation treatment. The Phase III study was published in the Journal of Clinical Oncology.

Zevalin significantly improved the median progression-free survival time from 13.3 months (control arm) to 36.5 months (treatment arm) (p<0.0001). This advantage was observed regardless of whether patients were in partial remission (29.3 v 6.2 months p<0.0001 without Zevalin) or complete remission (53.9 v 29.5 months p=0.0154).

Use of the drug converted 77 percent of patients who had achieved only a partial remission after induction therapy to complete remission / complete remission unconfirmed. Nearly all subgroups appeared to benefit regardless of prognostic score. The primary investigators of the study concluded that radioimmunotherapy with ibritumomab tiuxetan in advanced stage follicular non-Hodgkin's lymphoma is highly effective, resulting in a total complete response rate of 87 percent and prolongation of median progression-free survival by approximately two years.

The multinational, randomized phase III First-line Indolent Trial (FIT) evaluated the benefit and safety of a single infusion of Zevalin in 414 patients with CD20-positive follicular non-Hodgkin's lymphoma who had achieved a partial response or a complete response after receiving a variety of first-line chemotherapy regimens.

"Our results suggest that the use of high-dose Zevalin for these patients provides a significant clinical benefit and is very well tolerated," said Alessandro M. Gianni, M.D., Full Professor of Medical Oncology and Director of the School of Specialization in Medical Oncology at the University of Milan. "We are encouraged by the outcome of the study as this regimen could be applicable to the vast majority of high risk or relapsed non-Hodgkin's lymphoma patients."

High-dose Zevalin was well tolerated and no deaths were noted with this regimen. The expected severe marrow suppression associated with myeloablative treatment was seen but patients began to recover neutrophil and platelet counts within 3 weeks. Only minor non-hematologic toxicities were observed. Infections, none greater than grade 3, were noted in 8 patients (27 %) but hospitalization for grade 3 febrile neutropenia was required in only 3 patients. The authors concluded "the mild hematologic toxicity was unprecedented for a myeloablative regimen." The authors go on to state that "A notable and distinct difference in our study from virtually all other regimens of myeloablative polychemotherapy is the nearly complete absence of non- hematologic toxicity. Despite advanced age and presence of co-morbidities in many patients, none experienced vital organ toxicities of any grade. Mucositis, a major cause of toxicity and even infectious mortality after myeloablative treatments, was absent, and all patients were able to maintain normal oral intake of food and water. The excellent tolerability of myeloablative radioimmunotherapy was noteworthy in that 19 patients (63 percent) had previously not met the eligibility criteria for chemotherapy- based autotransplantation regimens as a result of elderly age and/or comorbidities."

A companion editorial discussed the growing evidence for the efficacy of radioimmunotherapy (RIT) in B-cell lymphomas. Oliver W. Press, M.D., Ph.D., Member of the Fred Hutchinson Cancer Research Center and Professor at the University of Washington, commented in his editorial that the studies "confirm and extend prior data demonstrating the tremendous potential of RIT in the treatment of B-cell NHL at diagnosis and after relapse at both conventional and myeloablative doses. Despite the overwhelming body of evidence, however, RIT remains underused in the United States and other countries. The reasons for this underuse have been widely debated but seem to be related, at least partially, to logistic issues involved in the transfer of care from the hematologist/oncologist to the nuclear medicine physician, concerns about inadequate reimbursement by Medicare for RIT, and exaggerated emphasis on delayed effects such as marrow damage and secondary malignancies. It is hoped that studies such as those in this issue would encourage wider appreciation and use of RIT."

Zevalin is currently approved in the United States for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL), including patients with rituximab refractory follicular NHL. The Zevalin therapeutic regimen has been given accelerated approval for the treatment of relapsed or refractory, rituximab-naive, low-grade and follicular NHL based on studies using an endpoint of overall response rate, which is a surrogate for progression free survival.