Abstract

CD20, a B-cell specific 297-amino acid transmembrane phosphoprotein and the target of the monoclonal antibody rituximab, is expressed at lower levels in malignant cells from patients with CLL as compared to other indolent B-cell malignancies. Anecdotal observations have suggested that CLL patients with trisomy 12 may have higher cell-surface CD20 expression than other cytogenetic subtypes. In order to test this hypothesis, we analyzed bone marrow (n=454) and peripheral blood (n=56) samples from 510 chemotherapy-naïve patients using a Vysis FISH panel and a flow cytometric quantitative CD20 antigen assay. FISH studies identified 99 patients (19%) with trisomy 12. Compared to non-trisomy 12 patients, patients with trisomy 12 were older (p=0.002) and were more likely to have increased serum B2-microglobulin (p<0.001), LDH (p<0.001), splenomegaly (p=0.007), and hepatomegaly (p=0.01). Mean CD20 antigen sites were significantly higher in patients with trisomy 12 in both peripheral blood and bone marrow samples (log mean 4.64 vs. 4.03 for PB, p<0.001; log mean 4.36 vs. 3.99 for BM, p<0.001). Mean CD20 antigen expression by Döhner subtypes were (per cell): trisomy 12 24,255; 17p deletion 11,114; negative FISH 10,557; 13q deletion 10,431; and 11q deletion 6,391. A multivariate analysis confirmed trisomy 12 as the only significant predictor of increased CD20 expression. To date, 11 CLL patients with trisomy 12 have received rituximab and GMCSF as initial therapy, and partial response was achieved in 8 of 9 (89%) assessable patients. Increased CD20 antigen expression in CLL patients with trisomy 12 provides a rationale for exploration of rituximab-based regimens in these patients.

Disclosures: The combination of GMCSF and rituxan is investigational.; Dr Keating is a consultant to Genentech and Berlex.; Dr Keating receives research funding from Genentech and Berlex. Dr O’Brien receives research funding from Genentech, Berlex and Biogen IDEC. Dr Ferrajoli and Dr Wierda receives research funding from Berlex.; Dr Keating receives honoraria from Genentech and Berlex.; Dr Keating is a member of the Speakers Bureau for Genentech and Berlex.

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