Universität zu Köln

Klanova, Magdalena, Oestergaard, Mikkel Z., Trneny, Marek, Hiddemann, Wolfgang, Marcus, Robert, Sehn, Laurie H., Vitolo, Umberto, Bazeos, Alexandra, Goede, Valentin, Zeuner, Harald, Knapp, Andrea, Sahin, Deniz, Spielewoy, Nathalie, Bolen, Christopher R., Cardona, Andres ORCID: 0000-0002-3873-0194, Klein, Christian, Venstrom, Jeffrey M., Nielsen, Tina and Fingerle-Rowson, Guenter (2019). Prognostic Impact of Natural Killer Cell Count in Follicular Lymphoma and Diffuse Large B-cell Lymphoma Patients Treated with Immunochemotherapy. Clin. Cancer Res., 25 (15). S. 4634 - 4644. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: Natural killer (NK) cells are key effector cells for anti-CD20 monoclonal antibodies (mAb), such as obinutuzumab and rituximab. We assessed whether low pretreatment NK-cell count (NKCC) in peripheral blood or tumor tissue was associated with worse outcome in patients receiving antibodybased therapy. Patients and Methods: Baseline peripheral blood NKCC was assessed by flow cytometry (CD3(-) CD56(+) and/or CD16(+) cells) in 1,064 of 1,202 patients with follicular lymphoma treated with obinutuzumab or rituximab plus chemotherapy in the phase III GALLIUM trial (NCT01332968) and 1,287 of 1,418 patients with diffuse large B-cell lymphoma (DLBCL) treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP or R-CHOP) in the phase III GOYA trial (NCT01287741). The prognostic value of tumor NK-cell gene expression, as assessed by whole-transcriptome gene expression using TruSeq RNA sequencing, was also analyzed. The association of baseline variables, such as treatment arm, was evaluated using multivariate Cox regression models using a stepwise approach. Results: In this exploratory analysis, low baseline peripheral blood NKCC was associated with shorter progression-free survival (PFS) in both follicular lymphoma [hazard ratio (HR), 1.48; 95% confidence interval (CI), 1.02-2.14; P = 0.04] and DLBCL (HR, 1.36; 95% CI, 1.01-1.83; P = 0.04), and overall survival in follicular lymphoma (HR, 2.20; 95% CI, 1.26-3.86; P = 0.0058). Low tumor NK-cell gene expression was associated with shorter PFS in G-CHOP-treated patients with DLBCL (HR, 1.95; 95% CI, 1.22-3.15; P < 0.01). Conclusions: These findings indicate that the number of NK cells in peripheral blood may affect the outcome of patients with B-cell non-Hodgkin lymphoma receiving anti-CD20 based immunochemotherapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klanova, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Oestergaard, Mikkel Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Trneny, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Hiddemann, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcus, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Sehn, Laurie H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vitolo, Umberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Bazeos, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Goede, Valentin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeuner, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Knapp, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahin, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Spielewoy, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolen, Christopher R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cardona, Andres UNSPECIFIED orcid.org/0000-0002-3873-0194 UNSPECIFIED Klein, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Venstrom, Jeffrey M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nielsen, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fingerle-Rowson, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-146017
DOI:	10.1158/1078-0432.CCR-18-3270
Journal or Publication Title:	Clin. Cancer Res.
Volume:	25
Number:	15
Page Range:	S. 4634 - 4644
Date:	2019
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PERIPHERAL-BLOOD; RITUXIMAB; CD20; CYTOTOXICITY; ANTIBODY; DIFFERENTIATION; OBINUTUZUMAB; MECHANISM; ARISE Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14601