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:
CreatorsEmailORCIDORCID Put Code
Klanova, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oestergaard, Mikkel Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trneny, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hiddemann, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marcus, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sehn, Laurie H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vitolo, UmbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bazeos, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goede, ValentinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeuner, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knapp, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahin, DenizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spielewoy, NathalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolen, Christopher R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cardona, AndresUNSPECIFIEDorcid.org/0000-0002-3873-0194UNSPECIFIED
Klein, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venstrom, Jeffrey M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nielsen, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fingerle-Rowson, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
PERIPHERAL-BLOOD; RITUXIMAB; CD20; CYTOTOXICITY; ANTIBODY; DIFFERENTIATION; OBINUTUZUMAB; MECHANISM; ARISEMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14601

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