Correlation of I-131 Tositumomab biodistribution and FDG PET positivity in patients treated with Bexxar for non-Hodgkins lymphoma

Abstract

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Objectives: It has been demonstrated that prolonged clinical remissions can be achieved when radioimmunotherapy with Bexxar is used in patients with relapsed or refractory Non-Hodgkin’s lymphoma (NHL). Our goal is to determine whether tumor targeting on dosimetry scans is a predictor of clinical response in these patients.

Methods: Of 12 patients treated for advanced stage relapsed or refractory NHL, 11 were evaluable with adequate follow-up. Six of the 11 patients had low grade follicular lymphoma, four had transformed follicular lymphoma, and one patient had a histologic diagnosis of MALT. Each patient received a single course of I-131 Tositumomab therapy (Bexxar). Tumor targeting was assessed by analysis of findings on baseline pre-treatment FDG PET and dosimetry scans. Extent of targeting on the I-131 scans was categorized as greater than, similar to, or less than the baseline FDG PET. Clinical response was also evaluated with a median follow-up of 5 months. A complete response was defined as complete disappearance of detectable disease by physical exam and FDG PET or CT of at least 12 week’s duration, partial response 50% reduction in measurable lesions and no new lesions, and progressive disease appearance of new lesions or more than 25% increase in size of existing lesions.

Results: In our subset of heavily pretreated patients, two had a complete response (18%), six had a partial response (55%), and three had progressive disease (27%). All patients with low grade lymphoma (without transformation) and evidence of antibody targeting of tumor greater than or similar to the baseline FDG PET had a complete or partial response (n=5). In contrast, only 3 of 6 patients with transformed histology or poor antibody targeting responded. Two of the responders demonstrated targeting of antibody in sites that did not metabolize FDG. Possible explanations for the discordant findings are as follows: 1. antibody targeting of CD20 positive cancer cells which have low metabolic activity 2. aggressive immune reaction to the tumor which suppresses its metabolic activity (dormant state) 3. nonspecific inflammatory changes that recruit normal B lymphocytes (false positive).

Conclusions: Patients with low grade (non-transformed) NHL who demonstrate tumor targeting on dosimetry scans greater than or similar to baseline FDG PET had better clinical outcomes in our small study population. Discordant findings between antibody scan and FDG PET can be explained by differences in the metabolic activity of the tumor, the degree of differentiation and neovascularization, and the associated immune reaction. Updated analysis with longer follow-up will be presented.