[1319] Persistent Tumor-Specific Expression of CD52 but Not CD20 Following Alemtuzumab and Rituximab Treatment in Chronic Lymphocytic Leukemia: Implications for Resistance to Antibody-Based Therapies

D Wu, JL Kutok, SJ Rodig. Brigham & Women's Hospital, Boston, MA

Background: Alemtuzumab (Campath) is a humanized monoclonal antibody that targets CD52, a GPI-linked glycoprotein expressed by B cells, T cells, monocytes and macrophages. Alemtuzumab is FDA-approved for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL), and its role in the treatment of other hematopoietic malignancies is being actively explored. We have previously reported a survey of CD52 expression among the various classes of hematopoietic neoplasms. However, the expression of CD52 in tumors that recur following alemtuzumab treatment has not been studied in detail. Knowledge of post-treatment expression of CD52 antigen may provide insight into mechanisms of tumor evasion and suggest optimal diagnostic approaches for monitoring response to therapy.
Design: Paraffin-archived bone marrow biopsies from twelve patients with recurrent/ relapsed CLL following treatment with both alemtuzumab and rituximab were retrieved from the Brigham and Women's Hospital repository. For five of the twelve patients, pre-treatment bone marrow biopsies were also available for study. Cases were stained using standard and published immunohistochemical methods (IHC) for CD52 and CD20. Cases were reviewed for antigen expression by two hematopathologist in a blinded fashion. Correlation with clinical records to determine treatment responses was then performed.
Results: CD52 and CD20 were expressed by all tumor cells prior to treatment- in agreement with prior reports. Among cases of recurrent/ relapsed CLL following treatment with both alemtuzumab and rituximab, 11 cases (92%) showed strong expression of CD52 indistinguishable from untreated tumor. One case showed heterogeneous expression of CD52 among the tumor cells. In contrast, all cases (100%) showed evidence for downregulation of CD20, with 11 of 12 cases (92%) showing undetectable CD20 by immunohistochemical techniques. Undetectable CD20 expression in these cases was also confirmed by flow cytometry.
Conclusions: Among patients with recurrent CLL after treatment with alemtuzumab and rituximab, there is a strong selection bias for tumor cells that downregulate the target antigen CD20; however, there is not a corresponding decrease in CD52 expression in these same tumor cells. These findings indicate that, within a single tumor type, there are distinct adaptive responses to individual antibody-based therapies and suggest the possibility of sustained sensitivity to alemtuzumab but not rituximab in relapsed disease.
Category: Hematopathology

Tuesday, March 10, 2009 9:30 AM

Poster Session III # 109, Tuesday Morning