Prognostic impact of natural killer cell count in follicular lymphoma and diffuse large B-cell lymphoma patients treated with immunochemotherapy

Clinical Cancer Research Online First Ar.. by Klanova, M., Oestergaard, M. Z., Tr.. - 59m ago Preview

 
 
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Purpose: Natural killer (NK) cells are key effector cells for anti-CD20 monoclonal antibodies,such as obinutuzumab (G) and rituximab (R). 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. Methods: Baseline peripheral blood NKCC was assessed by flow cytometry (CD3-CD56+ and/or CD16+ cells) in 1064/1202 follicular lymphoma (FL) patients treated with G or R plus chemotherapy in the phase III GALLIUM trial (NCT01332968) and 1287/1418 diffuse large B-cell lymphoma (DLBCL) patients treated with G or R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (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 PFS in both FL (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 OS in FL (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 DLBCL patients (HR, 1.95, 95% CI, 1.22-3.15, P < 0.01). Conclusion: These findings indicate that the number of NK cells in peripheral blood may affect the outcome of B-cell non-Hodgkin lymphoma patients receiving anti-CD20-based immunochemotherapy.