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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; Klein, Christian; Venstrom, Jeffrey M.; Nielsen, Tina; Fingerle-Rowson, Guenter (2019): Prognostic Impact of Natural Killer Cell Count in Follicular Lymphoma and Diffuse Large B-cell Lymphoma Patients Treated with Immunochemotherapy. In: Clinical Cancer Research, Vol. 25, No. 15: pp. 4634-4643
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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.