Abstract
PurposeTreatment of patients with diffuse large B cell lymphoma (DLBCL) includes rituximab, an anti-CD20 monoclonal antibody (mAb). Insufficient tumor targeting might cause therapy failure. Tumor uptake of 89Zirconium (89Zr)-mAb is a potential imaging biomarker for tumor targeting, since it depends on target antigen expression and accessibility. The aim of this pilot study was to describe the performance of 89Zr-labeled-rituximab-PET to assess CD20 targeting in patients with relapsed/refractory DLBCL.MethodsSix patients with biopsy-proven DLBCL were included. CD20 expression was assessed using immunohistochemistry (IHC). 74 MBq 89Zr-rituximab (10 mg) was administered after the therapeutic dose of rituximab. Immuno-PET scans on day 0, 3 and 6 post injection (D0, D3 and D6 respectively) were visually assessed and quantified for tumor uptake.ResultsTumor uptake of 89Zr-rituximab and CD20 expression were concordant in 5 patients: for one patient, both were negative, for the other four patients visible tumor uptake was concordant with CD20-positive biopsies. Intense tumor uptake of 89Zr-rituximab on PET (SUVpeak = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of 89Zr-rituximab (range SUVpeak = 3.2–5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of 89Zr-rituximab was observed (SUVpeak = 3.8), while the biopsy was CD20-negative.ConclusionsThis study suggests a positive correlation between tumor uptake of 89Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of 89Zr-rituximab-PET as an imaging biomarker for CD20 targeting. For clinical application of 89Zr-rituximab-PET to guide individualized treatment, further studies are required to assess whether tumor targeting is related to clinical benefit of rituximab treatment in individual patients.
Highlights
diffuse large B cell lymphoma (DLBCL) is an aggressive, potentially fatal, but curable form of lymphoma
Tumor uptake of 89Zr-rituximab and CD20 expression were concordant in 5 patients: for one patient, both were negative, for the other four patients visible tumor uptake was concordant with CD20-positive biopsies
This study suggests a positive correlation between tumor uptake of 89Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this
Summary
DLBCL is an aggressive, potentially fatal, but curable form of lymphoma. It is the most common lymphoma subtype, representing 30% of all lymphoma. An anti-CD20 mAb, is currently incorporated in all first line and subsequent treatment regimens for DLBCL. The introduction of rituximab in first line treatment has improved the prognosis of a three-year eventfree survival (EFS) from 59% to 79% for patients of 18 to 60 years old. Patients with relapsed/refractory DLBCL have a three-year overall survival (OS) of only 49% [1]. To obtain clinical benefit from mAb treatment tumor targeting is required. It comprises target antigen expression, as well as a drug that reaches and binds to the target
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