Ibritumomab: new drug. Interesting concept, disappointing in practice

(1) First-line standard chemotherapy for follicular non-Hodgkin's lymphoma is based on alkylating agents. For patients who relapse, rituximab, a monoclonal antibody targeting CD20 receptors on tumour cells, induces remissions lasting at least 9 months in about 50% of cases. However, the infusions are often poorly tolerated and reactions can be severe. (2) Ibritumomab is a monoclonal antibody similar to rituximab. It is not in itself cytotoxic. Yttrium-90-radiolabeled ibritumomab has been licensed in the EU since 2004 for local tumour radiotherapy, administered shortly after rituximab therapy. It is approved as a third-line treatment for follicular lymphoma, after rituximab failure. (3) The only available comparative trial, lasting 4 years, involved 143 patients who were treated either with rituximab followed by radiolabeled ibritumomab, or with rituximab alone. The sequential treatment yielded more tumour responses but the time to lymphoma progression and clinical outcomes did not differ between the two treatment groups. (4) In a non comparative trial about half the patients in whom rituximab had failed responded to rituximab + radiolabeled ibritumomab, but lymphoma progression occurred after a median of only 7 months. (5) Patients who receive sequential therapy with rituximab + ibritumomab are exposed to the adverse effects of rituximab plus supplementary gastrointestinal, respiratory, haematological and infectious risks, mainly due to persistent myelosuppression. (6) The radiation hazard for the patient (irradiation of healthy organs) and for the environment appears to be limited, because of the short reach of beta particle emission (5 mm) and the short half-life of yttrium 90 (2.7 days). (7) Yttrium 90 radiolabeling requires special equipment and specialised personnel working in an approved centre, which can restrict access to treatment. (8) Radiolabeled ibritumomab appears to have a negative risk-benefit balance, and should only be used in clinical trials.