Lee Vivian, Hultcrantz Malin, Petrone Stephanie, Lewis Eric W, Banna Hussam, Lichtman Eben, Thulasi Praneetha, Quick Anjulie A, Jeng Bennie H, Sunshine Sarah B, Francis Jasmine H, Canestraro Julia, Farooq Asim V, Clements Peter, Robertson Nicola, Burman Mark, McKevitt Tom, Struemper Herbert, Weir Lucinda
Department of Ophthalmology and Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Ophthalmol. 2025 May 8. doi: 10.1001/jamaophthalmol.2025.1008.
Ocular surface events are a class effect of microtubule-inhibitor payload-containing antibody-drug conjugates (ADCs); the mechanism underlying these events has not been fully elucidated.
To characterize corneal epithelial changes in patients with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin, a maleimidocaproyl monomethyl auristatin-F (MMAF)-containing ADC.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3b case series study was conducted in the US from March 26, 2020, to November 21, 2022, among adults with RRMM. Data were analyzed from May 2021 to May 2023.
Prior or ongoing treatment with belantamab mafodotin.
The primary end point included pathologic characteristics and composition of corneal epithelial changes obtained by impression cytology (IC) or superficial keratectomy (SK) in patients treated with belantamab mafodotin. Tear film and blood were collected to determine belantamab mafodotin concentrations in patients at the time of sampling.
Of 16 patients screened, 9 were included in this study, with 6 evaluable corneal samples obtained from 6 patients either by IC (n = 4) or SK (n = 2). Of 9 patients included, median (range) patient age was 67.0 (57.0-81.0) years for those with samples obtained by IC and 68.0 (65.0-81.0) years for those with samples obtained by SK. Six patients (67%) were female. All samples demonstrated epithelial cells with eosinophilic intracytoplasmic inclusions, basophilic granular cytoplasm, or both. Five samples were positive for apoptosis, and 3 samples showed evidence of inflammation. All patients experienced complete IC or SK wound healing. ADC was detected in the tear fluid of 5 of 7 patients with tear fluid sampling, while ADC was quantifiable in 3 of 4 patients with blood samples.
In this case series study, intracytoplasmic inclusions were observed by histopathology in the corneal epithelium of patients exposed to belantamab mafodotin, and the pattern of corneal changes suggests limbal vessels may be a primary pathway enabling ADC to reach the cornea. Although limited to 6 samples, this study helps us better understand corneal changes associated with certain ADCs.
ClinicalTrials.gov Identifier: NCT04549363.
眼表事件是含微管抑制剂有效载荷的抗体药物偶联物（ADC）的类效应；这些事件背后的机制尚未完全阐明。
描述接受贝兰他单抗马福多汀（一种含马来酰亚胺己酰单甲基奥瑞他汀-F（MMAF）的ADC）治疗的复发或难治性多发性骨髓瘤（RRMM）患者的角膜上皮变化。
设计、地点和参与者：这项多中心3b期病例系列研究于2020年3月26日至2022年11月21日在美国对RRMM成人患者进行。数据于2021年5月至2023年5月进行分析。
先前或正在接受贝兰他单抗马福多汀治疗。
主要终点包括通过印片细胞学检查（IC）或浅表角膜切除术（SK）获得的接受贝兰他单抗马福多汀治疗患者的角膜上皮变化的病理特征和组成。采集泪液和血液以测定患者采样时的贝兰他单抗马福多汀浓度。
在16名筛查患者中，9名被纳入本研究，从6名患者中通过IC（n = 4）或SK（n = 2）获得了6份可评估的角膜样本。在纳入的9名患者中，通过IC获得样本的患者中位（范围）年龄为67.0（57.0 - 81.0）岁，通过SK获得样本的患者为68.0（65.0 - 81.0）岁。6名患者（67%）为女性。所有样本均显示上皮细胞有嗜酸性胞质内包涵体、嗜碱性颗粒状细胞质或两者皆有。5份样本凋亡呈阳性，3份样本有炎症迹象。所有患者的IC或SK伤口均完全愈合。在7名进行泪液采样的患者中，5名患者的泪液中检测到ADC，而在4名进行血液采样的患者中，3名患者的ADC可定量。
在本病例系列研究中，通过组织病理学观察到暴露于贝兰他单抗马福多汀的患者角膜上皮中有胞质内包涵体，角膜变化模式表明角膜缘血管可能是使ADC到达角膜的主要途径。尽管本研究仅限于6份样本，但有助于我们更好地了解与某些ADC相关的角膜变化。
ClinicalTrials.gov标识符：NCT04549363。
