Epratuzumab Y-90

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.

Radioimmunotherapy (RIT) is a new treatment option for patients with non-Hodgkin lymphoma (NHL). Response to RIT currently remains difficult to predict using conventional prognostic factors and could be refined using functional imaging. The goal of this work is to evaluate the value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting response to Yttrium 90-labeled monoclonal antibodies for patients with NHL.

Thirty-five patients with NHL who had undergone (18)F-FDG PET prior to RIT with either (90)Y-ibritumomab tiuxetan (group A; n = 17) or (90)Y-epratuzumab tetraxetan (group B; n = 18) were included in this retrospective study. Four functional criteria were determined for each tumour lesion in a given patient: maximum and mean standard uptake values (SUVmax and SUVmean), functional lesion volume (LVol) and total lesion glycolysis (TLG, product of the volume and the SUVmean). For each patient, we determined highest SUVmax and SUVmean, cumulative TLG (TLGcum) and sum of all LVol (TVol) and compared their predictive value on response (complete or partial response according to IWC) to RIT with those of conventional prognostic factors in group A and B.

A total of 154 lesions were analysed. Nineteen patients (54%) responded to RIT according to IWC. In group A, response rate was 54, 75 and 75% in patients with a SUV max <20 g/ml, a TVol <100 ml and a TLGcum <1060 g, respectively while no patient above these thresholds responded (p < 0.005). In group B, the response rate was 93% for with SUVmax <15 g/ml while no patient above this threshold responded. With TLGcum below 1,360 g, 100% of the patient responded, compared with 37% of patients whose TLGcum was above this threshold (p < 0.05). By contrast, conventional prognostic factors failed to predict response.

Our preliminary results indicate that pre-therapy (18)F-FDG PET functional parameters such as SUVmax and TLG may help predicting more accurately response to single agent Y90 based RIT.