Klanova Magdalena, Oestergaard Mikkel Z, Trněný 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 Günter
Charles University General Hospital, Prague, Czech Republic.
Institute of Pathological Physiology, Charles University, Prague, Czech Republic.
Clin Cancer Res. 2019 Aug 1;25(15):4634-4643. doi: 10.1158/1078-0432.CCR-18-3270. Epub 2019 May 3.
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.
Baseline peripheral blood NKCC was assessed by flow cytometry (CD3CD56 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.
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; = 0.04] and DLBCL (HR, 1.36; 95% CI, 1.01-1.83; = 0.04), and overall survival in follicular lymphoma (HR, 2.20; 95% CI, 1.26-3.86; = 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; < 0.01).
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.
自然杀伤（NK）细胞是抗CD20单克隆抗体（mAb）如奥滨尤妥珠单抗和利妥昔单抗的关键效应细胞。我们评估了外周血或肿瘤组织中预处理时低自然杀伤细胞计数（NKCC）是否与接受基于抗体治疗的患者的较差预后相关。
在III期GALLIUM试验（NCT01332968）中，对1202例接受奥滨尤妥珠单抗或利妥昔单抗联合化疗的滤泡性淋巴瘤患者中的1064例，以及在III期GOYA试验（NCT01287741）中，对1418例接受奥滨尤妥珠单抗或利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（G-CHOP或R-CHOP）治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者中的1287例，通过流式细胞术（CD3-CD56和/或CD16细胞）评估基线外周血NKCC。还分析了通过使用TruSeq RNA测序进行全转录组基因表达评估的肿瘤NK细胞基因表达的预后价值。使用逐步方法的多变量Cox回归模型评估治疗组等基线变量的相关性。
在这项探索性分析中，低基线外周血NKCC与滤泡性淋巴瘤[风险比（HR），1.48；95%置信区间（CI），1.02-2.14；P = 0.04]和DLBCL（HR，1.36；95% CI，1.01-1.83；P = 0.04）的无进展生存期（PFS）缩短相关，并且与滤泡性淋巴瘤的总生存期（HR，2.20；95% CI，1.26-3.86；P = 0.0058）相关。在接受G-CHOP治疗的DLBCL患者中，低肿瘤NK细胞基因表达与较短的PFS相关（HR，1.95；95% CI，1.22-3.15；P < 0.01）。
这些发现表明外周血中NK细胞的数量可能影响接受基于抗CD20免疫化疗的B细胞非霍奇金淋巴瘤患者的预后。
