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- W4362551706 abstract "<div>Abstract<p>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) <i>CD47</i> mRNA expression correlated with a detrimental effect on overall survival (OS) when DLBCL patients received R-CHOP therapy (<i>P</i> = 0.001), but not CHOP therapy (<i>P</i> = 0.645). Accordingly, patients with low <i>CD47</i> expression benefited most from the addition of rituximab to CHOP [HR, 0.32; confidence interval (CI), 0.21–0.50; <i>P</i> < 0.001]. This negative impact of high <i>CD47</i> expression on OS after R-CHOP treatment was only evident in cancers of non-GCB origin (HR, 2.09; CI, 1.26–3.47; <i>P</i> = 0.004) and not in the GCB subtype (HR, 1.16; CI, 0.68–1.99; <i>P</i> = 0.58). This differential impact of <i>CD47</i> in non-GCB and GCB was confirmed <i>in vitro</i>, as macrophage-mediated phagocytosis stimulated by rituximab was augmented by CD47-blocking antibody only in non-GCB cell lines. Thus, high expression of <i>CD47</i> 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.</p></div>" @default.
- W4362551706 created "2023-04-06" @default.
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- W4362551706 date "2023-04-04" @default.
- W4362551706 modified "2023-10-16" @default.
- W4362551706 title "Data from 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" @default.
- W4362551706 doi "https://doi.org/10.1158/2326-6066.c.6549826" @default.
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