Yttrium ibritumomab tiuxetan in the treatment of non-Hodgkin's lymphoma: current status and future prospects

Abstract

After nearly three decades with little change in the treatment for B-cell non-Hodgkin's lymphoma, the addition of immunotherapy has had a profound effect on the treatment of this group of diseases. A more subtle addition to the armentarium has been the radiolabeled monoclonal antibodies, (90)yttrium ibritumomab tiuxetan and (131)iodine tositumomab. Unfortunately these drugs have been underutilized. This is, in part, because of the need for coordination between specialties, concern about long-term effects, possible limitations on the tolerance of subsequent therapies and, in part, because of reimbursement factors. In this review, the studies in relapsed and refractory disease are discussed and the very promising results reported from phase II studies using radioimmunotherapy as first-line. Potential mechanisms of resistance to monoclonal antibodies are postulated based on alterations in cell signaling pathways that have been observed in lymphoma cell lines resistant to rituximab. It is anticipated that as mechanisms of resistance are better understood for both unlabeled and labeled monoclonal antibodies, biomarkers will not only predict their efficacy but also lead to the development of therapies to overcome resistance.

Keywords: ibritumomab; immunotherapy; non-Hodgkin lymphoma; radioimmunotherapy; zevalin.

Figure 1

Autoradiographic localization of ⁹⁰Y-ibritumomab tiuxetan from lymph node on a patient sampled 4 days after treatment.

Figure 2

Panel 1 shows large left lung mass on CT scan with corresponding FDG-avidity, biopsy proven follicular lymphoma. Panel 2, 3 months later shows resolution of mass on CT scan and FDG-negative scan. Panel 3, 12 months after ⁹⁰Y-ibritumomab tiuextan shows infiltrative mass on CT scan and FDG-avid area apart from the heart. Bronchoscopy was negative for recurrent lymphoma and cultures were negative. Panel 4, 24 months after treatment there is residual scarring with decreased FDG-avidity.

Figure 3

CT scan with moderate pleural effusion and small pericardial effusion in patient with serum-sickness like syndrome. Both effusions rapidly cleared with steroid administration.

Figure 4

Graphs of sed rate and c-reative protein in patient with serum-sickness like syndrome following immunotherapy with ibritumomab aand rituximab. The rise in inflammatory markers corresponded with attempts at tapering of the dose of steroid.