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CD47 Expression Defines Efficacy of Rituximab with CHOP in Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

Bouwstra, R., He, Y., de Boer, J. W., Kooistra, H., Cendrowicz, E., Fehrmann, R. S. N., Ammatuna, E., Eulenburg, C., Nijland, M., Huls, G., Bremer, E. & van Meerten, T., Oct-2019, In : Cancer immunology research. 7, 10, p. 1663-1671 9 p.

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  • CD47 expression defines efficacy of rituximab with CHOP in Non-Germinal Center B-cell (non-GCB) Diffuse Large B-Cell Lymphoma patients (DLBCL), but not in GCB DLBCL

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  • CD47 Expression Defines Efficacy of Rituximab with CHOP in Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

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DOI

Addition of rituximab (R) to "CHOP" (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improved outcome for diffuse large B-cell lymphoma (DLBCL) patients. Approximately 40% of patients who receive R-CHOP still succumb to disease due to intrinsic resistance or relapse. A potential negative regulator of DLBCL treatment outcome is the CD47 "don't eat me" immune checkpoint. To delineate the impact of CD47, we used a clinically and molecularly well-annotated cohort of 939 DLBCL patients, comprising both germinal center B-cell (GCB) and non-GCB DLBCL subtypes, treated with either CHOP or R-CHOP. High (above median) CD47 mRNA expression correlated with a detrimental effect on overall survival (OS) when DLBCL patients received R-CHOP therapy (P = 0.001), but not CHOP therapy (P = 0.645). Accordingly, patients with low CD47 expression benefited most from the addition of rituximab to CHOP [HR, 0.32; confidence interval (CI), 0.21-0.50; P <0.001]. This negative impact of high CD47 expression on OS after R-CHOP treatment was only evident in cancers of non-GCB origin (HR, 2.09; CI, 1.26-3.47; P = 0.004) and not in the GCB subtype (HR, 1.16; CI, 0.68-1.99; P = 0.58). This differential impact of CD47 in non-GCB and GCB was confirmed in vitro, as macrophage-mediated phagocytosis stimulated by rituximab was augmented by CD47-blocking antibody only in non-GCB cell lines. Thus, high expression of CD47 mRNA limited the benefit of addition of rituximab to CHOP in non-GCB patients, and CD47-blockade only augmented rituximab-mediated phagocytosis in non-GCB cell lines. Patients with non-GCB DLBCL may benefit from CD47-targeted therapy in addition to rituximab.

Original languageEnglish
Pages (from-to)1663-1671
Number of pages9
JournalCancer immunology research
Volume7
Issue number10
Early online date13-Aug-2019
Publication statusPublished - Oct-2019

    Keywords

  • TUMOR-CELLS, MONOCLONAL-ANTIBODY, POOR-PROGNOSIS, OPEN-LABEL, PHAGOCYTOSIS, OVEREXPRESSION, CHEMOTHERAPY, MULTICENTER, MACROPHAGES, MECHANISMS

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