Publication

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.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Bouwstra, R., He, Y., de Boer, J. W., Kooistra, H., Cendrowicz, E., Fehrmann, R. S. N., ... van Meerten, T. (2019). 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. Cancer immunology research, 7(10), 1663-1671. https://doi.org/10.1158/2326-6066.CIR-18-0781

Author

Bouwstra, Renee ; He, Yuan ; de Boer, Janneke Willemien ; Kooistra, Hilde ; Cendrowicz, Ewa ; Fehrmann, Rudolf S N ; Ammatuna, Emanuele ; Eulenburg, Christine ; Nijland, Marcel ; Huls, Gerwin ; Bremer, Edwin ; van Meerten, Tom. / 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. In: Cancer immunology research. 2019 ; Vol. 7, No. 10. pp. 1663-1671.

Harvard

Bouwstra, R, He, Y, de Boer, JW, Kooistra, H, Cendrowicz, E, Fehrmann, RSN, Ammatuna, E, Eulenburg, C, Nijland, M, Huls, G, Bremer, E & van Meerten, T 2019, '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', Cancer immunology research, vol. 7, no. 10, pp. 1663-1671. https://doi.org/10.1158/2326-6066.CIR-18-0781

Standard

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, Renee; He, Yuan; de Boer, Janneke Willemien; Kooistra, Hilde; Cendrowicz, Ewa; Fehrmann, Rudolf S N; Ammatuna, Emanuele; Eulenburg, Christine; Nijland, Marcel; Huls, Gerwin; Bremer, Edwin; van Meerten, Tom.

In: Cancer immunology research, Vol. 7, No. 10, 10.2019, p. 1663-1671.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Bouwstra R, He Y, de Boer JW, Kooistra H, Cendrowicz E, Fehrmann RSN et al. 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. Cancer immunology research. 2019 Oct;7(10):1663-1671. https://doi.org/10.1158/2326-6066.CIR-18-0781


BibTeX

@article{863cd4677e2149348b4142bd5998186b,
title = "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",
abstract = "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.",
keywords = "TUMOR-CELLS, MONOCLONAL-ANTIBODY, POOR-PROGNOSIS, OPEN-LABEL, PHAGOCYTOSIS, OVEREXPRESSION, CHEMOTHERAPY, MULTICENTER, MACROPHAGES, MECHANISMS",
author = "Renee Bouwstra and Yuan He and {de Boer}, {Janneke Willemien} and Hilde Kooistra and Ewa Cendrowicz and Fehrmann, {Rudolf S N} and Emanuele Ammatuna and Christine Eulenburg and Marcel Nijland and Gerwin Huls and Edwin Bremer and {van Meerten}, Tom",
note = "Copyright {\circledC}2019, American Association for Cancer Research.",
year = "2019",
month = "10",
doi = "10.1158/2326-6066.CIR-18-0781",
language = "English",
volume = "7",
pages = "1663--1671",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "AMER ASSOC CANCER RESEARCH",
number = "10",

}

RIS

TY - JOUR

T1 - 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

AU - Bouwstra, Renee

AU - He, Yuan

AU - de Boer, Janneke Willemien

AU - Kooistra, Hilde

AU - Cendrowicz, Ewa

AU - Fehrmann, Rudolf S N

AU - Ammatuna, Emanuele

AU - Eulenburg, Christine

AU - Nijland, Marcel

AU - Huls, Gerwin

AU - Bremer, Edwin

AU - van Meerten, Tom

N1 - Copyright ©2019, American Association for Cancer Research.

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - TUMOR-CELLS

KW - MONOCLONAL-ANTIBODY

KW - POOR-PROGNOSIS

KW - OPEN-LABEL

KW - PHAGOCYTOSIS

KW - OVEREXPRESSION

KW - CHEMOTHERAPY

KW - MULTICENTER

KW - MACROPHAGES

KW - MECHANISMS

U2 - 10.1158/2326-6066.CIR-18-0781

DO - 10.1158/2326-6066.CIR-18-0781

M3 - Article

VL - 7

SP - 1663

EP - 1671

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6066

IS - 10

ER -

ID: 93870635