Lindgren Ethan S, Yan Rongshan, Cil Onur, Verkman Alan S, Chan Matilda F, Seitzman Gerami D, Farooq Asim V, Huppert Laura A, Rugo Hope S, Pohlmann Paula R, Lu Janice, Esserman Laura J, Pasricha Neel D
Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Curr Ophthalmol Rep. 2024 Jun;12(2):13-22. doi: 10.1007/s40135-024-00322-5. Epub 2024 Mar 24.
This study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).
ADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity.
Three of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.
本研究旨在强调美国食品药品监督管理局(FDA)批准的抗体药物偶联物(ADC)中角膜假性微囊肿的发生率,以及针对假性微囊肿和相关眼表不良事件(AE)的预防治疗的成效。
ADC是一类新兴的选择性癌症治疗药物,由一种强效细胞毒素与一种靶向恶性细胞上表达抗原的单克隆抗体(mAb)连接而成。目前,有11种FDA批准的ADC,超过164种正处于临床试验阶段。多种AE已归因于ADC,包括眼表AE(角膜炎/角膜病变、干眼、结膜炎、视力模糊、角膜假性微囊肿)。虽然ADC引起的眼表AE的严重程度和发生率已有充分报道,但角膜假性微囊肿的报道有限,这使得预防或治疗与ADC相关的眼表毒性的治疗方法的开发变得复杂。
11种FDA批准的ADC中有3种与角膜假性微囊肿有关,患者发生率在41%至100%之间。在报告了眼表AE的6种ADC中,只有3种进行了眼部亚研究,以调查包括局部类固醇、血管收缩剂和无防腐剂润滑剂在内的预防治疗的益处。目前的预防治疗在减轻假性微囊肿和其他眼表AE方面疗效有限。