Antibody-drug conjugate (ADC) drugs is a kind of antitumor drug with the unique mechanism and have become the focus and hotspots in the field of cancer. Ocular toxicity is one of the characteristic adverse events of ADC drugs in clinical studies. Although most ocular events are mild and reversible, the course of treatment may be affected in some patients. Therefore, the U.S. Food and Drug Administration requires that a black box warning of ocular toxicity to be added into the instruction of such drugs. In this study, we summarized the epidemiology, clinical manifestations, potential mechanism and prevention and treatment strategies in order to increase the awareness about ocular toxicity associated with ADC for clinicians, and provide references for individualized risk assessment, early diagnosis and medical management of ADC drugs.

1.Hafeez U, Parakh S, Gan HK, et al. Antibody-drug conjugates for cancer therapy[J]. Molecules, 2020, 25(20): 4764. DOI: 10.3390/molecules25204764.

2.Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer[J]. Drug Saf, 2019, 42(2): 295-314. DOI: 10.1007/s40264-018-0775-7.

3.Fu Z, Li S, Han S, et al. Antibody drug conjugate: the "biological missile" for targeted cancer therapy[J]. Signal Transduct Target Ther, 2022, 7(1): 93. DOI: 10.1038/s41392-022-00947-7.

4.季双敏, 王玉珠, 杨进波. 抗体偶联药物的分子特点及其药代动力学研究考虑[J]. 中国临床药理学杂志, 2021, 37(6): 777-782. [Ji SM, Wang YZ, Yang JB. Characteristics and consideration for pharmacokinetics of antibody-drug conjugates[J]. Chinese Journal of Clinical Pharmacology, 2021, 37(6): 777-782.] DOI: 10.13699/j.cnki.1001-6821.2021.06.033.

5.Malik P, Phipps C, Edginton A, et al. Pharmacokinetic considerations for antibody-drug conjugates against Cancer[J]. Pharm Res, 2017, 34(12): 2579-2595. DOI: 10.1007/s11095-017-2259-3.

6.Masters JC, Nickens DJ, Xuan D, et al. Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads[J]. Invest New Drugs, 2018, 36(1): 121-135. DOI: 10.1007/s10637-017-0520-6.

7.Zhu Y, Liu K, Wang K, et al. Treatment-related adverse events of antibody-drug conjugates in clinical trials: a systematic review and meta-analysis[J]. Cancer, 2023, 129(2): 283-295. DOI: 10.1002/cncr.34507.

8.Markham A. Belantamab mafodotin: first approval[J]. Drugs, 2020, 80(15): 1607-1613. DOI: 10.1007/s40265-020-01404-x.

9.Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study[J]. Lancet Oncol, 2020, 21(2): 207-221. DOI: 10.1016/S1470-2045(19)30788-0.

10.Coleman RL, Lorusso D, Gennigens C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study[J]. Lancet Oncol, 2021, 22(5): 609-619. DOI: 10.1016/S1470-2045(21)00056-5.

11.Yonemori K, Kuboki Y, Hasegawa K, et al. Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: results from the innovaTV 206 study[J]. Cancer Sci, 2022, 113(8): 2788-2797. DOI: 10.1111/cas.15443.

12.Moore KN, Oza AM, Colombo N, et al. Phase Ⅲ, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD Ⅰ[J]. Ann Oncol, 2021, 32(6): 757-765. DOI: 10.1016/j.annonc. 2021.02.017.

13.Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA Study[J]. J Clin Oncol, 2023, 41(13): 2436-2445. DOI: 10.1200/JCO.22.01900.

14.Shragai T, Magen H, Lavi N, et al. Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: a multicentre retrospective study[J]. Br J Haematol, 2023, 200(1): 45-53. DOI: 10.1111/bjh.18479.

15.Mohan M, Rein LE, Thalambedu N, et al. Corneal toxicity with belantamab mafodotin: multi-institutional real-life experience[J]. Am J Hematol, 2022, 97(12): E451-E453. DOI: 10.1002/ajh.26728.

16.Eaton JS, Miller PE, Mannis MJ, et al. Ocular adverse events associated with antibody-drug conjugates in human clinical trials[J]. J Ocul Pharmacol Ther, 2015, 31(10): 589-604. DOI: 10.1089/jop.2015.0064.

17.National Cancer Institute. Common terminology criteria for adverse events (CTCAE v5.0)[EB/OL]. (2017-11-27) [2023-01-11]. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_V5_Quick_Reference_5x7.pdf.

18.Donaghy H. Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates[J]. MAbs, 2016, 8(4): 659-671. DOI: 10.1080/ 19420862.2016.1156829.

19.Farooq AV, Degli Esposti S, Popat R, et al. Corneal epithelial findings in patients with multiple myeloma treated with antibody-drug conjugate belantamab mafodotin in the pivotal, randomized, DREAMM-2 Study[J]. Ophthalmol Ther, 2020, 9(4): 889-911. DOI: 10.1007/s40123-020-00280-8.

20.Matulonis UA, Birrer MJ, O'Malley DM, et al. Evaluation of prophylactic corticosteroid eye drop use in the management of corneal abnormalities induced by the antibody-drug conjugate mirvetuximab soravtansine[J]. Clin Cancer Res, 2019, 25(6): 1727-1736. DOI: 10.1158/1078-0432.CCR-18-2474.

21.Canestraro J, Hultcrantz M, Modi S, et al. Refractive shifts and changes in corneal curvature associated with antibody-drug conjugates[J]. Cornea, 2022, 41(6): 792-801. DOI: 10.1097/ICO.0000000000002934.

22.Jain N, Smith SW, Ghone S, et al. Current ADC linker chemistry[J]. Pharm Res, 2015, 32(11): 3526-40. DOI: 10.1007/s11095-015-1657-7.

23.Kim SK, Ursell P, Coleman RL, et al. Mitigation and management strategies for ocular events associated with tisotumab vedotin[J]. Gynecol Oncol, 2022, 165(2): 385-392. DOI: 10.1016/j.ygyno.2022.02.010.

24.Hong DS, Concin N, Vergote I, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer[J]. Clin Cancer Res, 2020, 26(6): 1220-1228. DOI: 10.1158/1078-0432.CCR-19-2962.