Radioimmunotherapy in follicular lymphoma

The exquisite sensitivity of haematological malignancies to targeted radiation make Radioimmunotherapy (RIT) a theoretically attractive therapeutic approach. Furthermore, impressive results initially achieved by the pioneers in this field and more recently in larger studies have demonstrated the high clinical activity of RIT in follicular NHL (FL). For more than a decade clinical RIT of FL has been dominated by targeting the CD20 antigen and a number of pivotal clinical studies have resulted in the approval by the US FDA (Food and Drug Administration) of two radioimmunconjugates, (131)I-tositumomab (Bexxar) and (90)Y-ibritumomab (Zevalin). (90)Y-ibritumomab tiuxetan was subsequently approved within the EU in 2004 and more recently in the EU and in the US as a front line "consolidation" treatment in follicular NHL. Recent data have demonstrated that fractionated radioimmunotherapy targeting CD22 with (90)Y-epratuzumab tetraxetan achieved a high degree of durable complete responses in relapsed/refractory NHL. Despite the fact that these RIT agents clearly have unique non-cross reactive mechanisms of action with proven high clinical efficacy in patients resistant to both chemotherapy and rituximab, they have not been widely adopted by haemato-oncology community to date. This chapter reviews the progress that has been made in the development of clinical radioimmunotherapy in follicular lymphoma and suggest some guidelines to use it appropriately in first-line but also in the increasing number of patients emerging who are rituximab-refractory.