Phillips Therese, Millett Molly M, Zhang Xiaoling, Jansson Malinka, Cleveland Rachel, Simmons Pauline, Cherryholmes Gregory, Carnahan Josette, William Josette, Spaulding Betsy, Satnick Ilana R, Inzunza H David, Taylor Clive, Cogswell John, Novotny James, Oroudjev Emin, Winther Henrik
Agilent Technologies, Santa Clara.
Spaulding Science Group, Santa Barbara.
Appl Immunohistochem Mol Morphol. 2018 Jan;26(1):6-12. doi: 10.1097/PAI.0000000000000605.
Nivolumab is a monoclonal antibody that blocks the interaction between programmed cell death 1 (PD1) and programmed cell death 1-ligand 1 (PD-L1), resulting in enhanced antitumor activity by the immune system. Nivolumab is currently approved by the US Food and Drug Administration (FDA) for melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. PD-L1 IHC 28-8 pharmDx is FDA-approved as a complementary diagnostic for immunohistochemical (IHC) detection of PD-L1 in non-squamous NSCLC and melanoma. We report validation of PD-L1 IHC 28-8 pharmDx for PD-L1 detection on formalin-fixed, paraffin-embedded human melanoma specimens using Autostainer Link 48. A prevalence assessment of 104 melanoma specimens indicated that PD-L1 was detected across the full expression level range (0% to 100% of tumor cells). Assay robustness and precision studies were conducted at Agilent Technologies, with additional reproducibility studies performed at 3 external laboratories. Precision studies evaluated at ≥1% and ≥5% expression levels revealed a range of average negative agreement from 89.5%, 95% CI (83.2, 93.6) to 100%, 95% CI (97.3, 100), and average positive agreement from 85.5%, 95% CI (77.6, 90.9) to 100%, 95% CI (97.9, 100). For external reproducibility, precise results were obtained. These results demonstrate PD-L1 IHC 28-8 pharmDx is a precise, robust, and reproducible assay for determining PD-L1 expression in melanoma. This is the first PD-L1 IHC test to receive FDA approval as a complementary diagnostic in melanoma patients whereby positive PD-L1 expression is correlated with the magnitude of nivolumab treatment effect.
纳武单抗是一种单克隆抗体，可阻断程序性细胞死亡蛋白1（PD1）与程序性细胞死亡蛋白1配体1（PD-L1）之间的相互作用，从而增强免疫系统的抗肿瘤活性。纳武单抗目前已获美国食品药品监督管理局（FDA）批准，用于治疗黑色素瘤、非小细胞肺癌（NSCLC）、肾细胞癌、经典型霍奇金淋巴瘤、头颈部鳞状细胞癌和尿路上皮癌。PD-L1 IHC 28-8 pharmDx已获FDA批准，作为非鳞状NSCLC和黑色素瘤中PD-L1免疫组织化学（IHC）检测的补充诊断方法。我们报告了使用Autostainer Link 48在福尔马林固定、石蜡包埋的人黑色素瘤标本上对PD-L1 IHC 28-8 pharmDx进行PD-L1检测的验证。对104份黑色素瘤标本的患病率评估表明，在整个表达水平范围（0%至100%的肿瘤细胞）内均检测到了PD-L1。在安捷伦科技公司进行了分析稳健性和精密度研究，并在3个外部实验室进行了额外的重现性研究。在≥1%和≥5%表达水平下评估的精密度研究显示，平均阴性一致性范围为89.5%，95%CI（83.2，93.6）至100%，95%CI（97.3，100），平均阳性一致性范围为85.5%，95%CI（77.6，90.9）至100%，95%CI（97.9，100）。对于外部重现性，获得了精确的结果。这些结果表明，PD-L1 IHC 28-8 pharmDx是一种精确、稳健且可重现的检测方法，用于确定黑色素瘤中PD-L1的表达。这是首个获得FDA批准作为黑色素瘤患者补充诊断的PD-L1 IHC检测方法，其中PD-L阳性表达与纳武单抗治疗效果的大小相关。
