Abstract

<div>AbstractPurpose:<p>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 antibody-based therapy.</p>Patients and Methods:<p>Baseline peripheral blood NKCC was assessed by flow cytometry (CD3<sup>−</sup>CD56<sup>+</sup> and/or CD16<sup>+</sup> 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.</p>Results:<p>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; <i>P</i> = 0.04] and DLBCL (HR, 1.36; 95% CI, 1.01–1.83; <i>P</i> = 0.04), and overall survival in follicular lymphoma (HR, 2.20; 95% CI, 1.26–3.86; <i>P</i> = 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; <i>P</i> < 0.01).</p>Conclusions:<p>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.</p></div>

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