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Sa H-S, Daniel C, Esmaeli B. Update on Immune Checkpoint Inhibitors for Conjunctival Melanoma. JOVR [Internet]. 2022Aug.9 [cited 2024Apr.19];17(3):405–412. Available from: https://knepublishing.com/index.php/JOVR/article/view/11579
https://doi.org/10.18502/jovr.v17i3.11579
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authors
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Ho-Seok Sa
Ho-Seok Sa
Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Claire Daniel
Claire Daniel
Moorfields Eye Hospital, National Health System, London, United Kingdom
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Bita Esmaeli
Bita Esmaeli
Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Published Date
- Aug 9, 2022
Update on Immune Checkpoint Inhibitors for Conjunctival Melanoma
Abstract
The management of conjunctival melanoma is challenging due to the more frequent local recurrence and metastasis compared to other conjunctival neoplasms. Locally advanced conjunctival melanoma may require an orbital exenteration, and treatment options for metastatic conjunctival melanoma have been limited until recently. This review aims to provide comprehensive updates on immunotherapy for conjunctival melanoma, focusing on immune checkpoint inhibitors. We reviewed the available literature on the use of immunotherapy for the treatment of conjunctival melanoma. Systemic immunotherapy, particularly with checkpoint inhibitors, has recently been reported to have improved outcomes for patients with conjunctival melanoma. Immune checkpoint inhibitors that are currently approved by the US Food and Drug Administration for melanoma include anti-PD-1 (nivolumab and pembrolizumab), anti- PDL-1 (avelumab and atezolizumab), and anti-CTLA-4 inhibitors (ipilimumab). Most recent reports described using immune checkpoint inhibitors in patients with locally advanced conjunctival melanoma in an attempt to avoid orbital exenteration or in patients with metastatic conjunctival melanoma. Although the current data are limited to case reports and small case series, eye care providers should be aware of the potential role of immunotherapy for patients with locally advanced, recurrent, or metastatic conjunctival melanoma.
Keywords:
Checkpoint Inhibitor, Conjunctival Neoplasm, Immunotherapy, Melanoma
References
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11. Paridaens AD, Minassian DC, McCartney AC, Hungerford JL. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994;78:252–259.
12. Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, Colin E, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open 2017;2:e000213.
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19. Ford J, Thuro BA, Thakar S, Hwu WJ, Richani K, Esmaeli B. Immune checkpoint inhibitors for treatment of metastatic melanoma of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg 2017;33:e82–e85.
20. Sagiv O, Thakar SD, Kandl TJ, Ford J, Sniegowski MC, Hwu WJ, et al. Immunotherapy with programmed cell death 1 inhibitors for 5 patients with conjunctival melanoma. JAMA Ophthalmol 2018;136:1236–1241.
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24. Cao J, Brouwer NJ, Richards KE, Marinkovic M, van Duinen S, Hurkmans D, et al. PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma. Oncotarget 2017;8:54722–54734.
25. Brouwer NJ, Verdijk RM, Heegaard S, Marinkovic M, Esmaeli B, Jager MJ. Conjunctival melanoma: New insights in tumour genetics and immunology, leading to new therapeutic options. Prog Retin Eye Res 2022;86:100971.
26. Kini A, Fu R, Compton C, Miller DM, Ramasubramanian A. Pembrolizumab for recurrent conjunctival melanoma. JAMA Ophthalmol 2017;135:891–892.
27. Pinto Torres S, André T, Gouveia E, Costa L, Passos MJ. Systemic treatment of metastatic conjunctival melanoma. Case Rep Oncol Med 2017;2017:4623964.
28. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723.
29. Chaves LJ, Huth B, Augsburger JJ, Correa ZM. Eye-sparing treatment for diffuse invasive conjunctival melanoma. Ocul Oncol Pathol 2018;4:261–266.
30. Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist 2016;21:634–642.
31. Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 2018;19:1480–1492.
32. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521–2532.
2. Al Bayyat G, Arreaza-Kaufman D, Venkateswaran N, Galor A, Karp CL. Update on pharmacotherapy for ocular surface squamous neoplasia. Eye Vis 2019;6:24.
3. Shields CL, Markowitz JS, Belinsky I, Schwartzstein H, George NS, Lally SE, et al. Conjunctival melanoma: Outcomes based on tumor origin in 382 consecutive cases. Ophthalmology 2011;118:389–395.e381–382.
4. Seregard S. Conjunctival melanoma. Surv Ophthalmol 1998;42:321–350.
5. Esmaeli B, Wang X, Youssef A, Gershenwald JE. Patterns of regional and distant metastasis in patients with conjunctival melanoma: Experience at a cancer center over four decades. Ophthalmology 2001;108:2101–2105.
6. Shields CL, Shields JA. Tumors of the conjunctiva and cornea. Indian J Ophthalmol 2019;67:1930–1948.
7. Lu JE, Chang JR, Berry JL, In GK, Zhang-Nunes S. Clinical update on checkpoint inhibitor therapy for conjunctival and eyelid melanoma. Int Ophthalmol Clin 2020;60:77–89.
8. Esmaeli B, Rubin ML, Xu S, Goepfert RP, Curry JL, Prieto VG, et al. Greater tumor thickness, ulceration, and positive sentinel lymph node are associated with worse prognosis in patients with conjunctival melanoma: Implications for future AJCC classifications. Am J Surg Pathol 2019;43:1701–1710.
9. Grimes JM, Shah NV, Samie FH, Carvajal RD, Marr BP. Conjunctival melanoma: Current treatments and future options. Am J Clin Dermatol 2020;21:371–381.
10. Jain P, Finger PT, Fili M, Damato B, Coupland SE, Heimann H, et al. Conjunctival melanoma treatment outcomes in 288 patients: A multicentre international data-sharing study. Br J Ophthalmol 2020;105:1358–1364.
11. Paridaens AD, Minassian DC, McCartney AC, Hungerford JL. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994;78:252–259.
12. Granier C, De Guillebon E, Blanc C, Roussel H, Badoual C, Colin E, et al. Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. ESMO Open 2017;2:e000213.
13. Esmaeli B, Sagiv O. Targeted biological drugs and immune check point inhibitors for locally advanced or metastatic cancers of the conjunctiva, eyelid, and orbit. Int Ophthalmol Clin 2019;59:13–26.
14. US-FDA. FDA labeling information - YERVOY. FDA website; 2015. Available from: https://www.accessdata. fda.gov/drugsatfda_docs/label/2015/125377s074lbl.pdf
15. US-FDA. FDA labeling information - OPDIVO. FDA website; 2017. Available from: https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/125554s024lbl.pdf
16. US-FDA. FDA labeling information - KEYTRUDA. FDA website; 2017. Available from: https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/125514s015lbl.pdf
17. US-FDA. FDA labeling information - BAVENCIO. FDA website; 2017. Available from: https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/761049s000lbl.pdf
18. Rossi E, Schinzari G, Maiorano BA, Indellicati G, Di Stefani A, Pagliara MM, et al. Efficacy of immune checkpoint inhibitors in different types of melanoma. Hum Vaccin Immunother 2021;17:4–13.
19. Ford J, Thuro BA, Thakar S, Hwu WJ, Richani K, Esmaeli B. Immune checkpoint inhibitors for treatment of metastatic melanoma of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg 2017;33:e82–e85.
20. Sagiv O, Thakar SD, Kandl TJ, Ford J, Sniegowski MC, Hwu WJ, et al. Immunotherapy with programmed cell death 1 inhibitors for 5 patients with conjunctival melanoma. JAMA Ophthalmol 2018;136:1236–1241.
21. Hong BY, Ford JR, Glitza IC, Torres Cabala CA, Tetzlaff M, Prieto VG, et al. Immune checkpoint inhibitor therapy as an eye-preserving treatment for locally advanced conjunctival melanoma. Ophthal Plast Reconstr Surg 2021;37:e9–e13.
22. Finger PT, Pavlick AC. Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: A clinical case series. J Immunother Cancer 2019;7:83.
23. Rossi E, Schinzari G, Maiorano BA, Pagliara MM, Di Stefani A, Bria E, et al. Conjunctival melanoma: Genetic and epigenetic insights of a distinct type of melanoma. Int J Mol Sci 2019;20:E5447.
24. Cao J, Brouwer NJ, Richards KE, Marinkovic M, van Duinen S, Hurkmans D, et al. PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma. Oncotarget 2017;8:54722–54734.
25. Brouwer NJ, Verdijk RM, Heegaard S, Marinkovic M, Esmaeli B, Jager MJ. Conjunctival melanoma: New insights in tumour genetics and immunology, leading to new therapeutic options. Prog Retin Eye Res 2022;86:100971.
26. Kini A, Fu R, Compton C, Miller DM, Ramasubramanian A. Pembrolizumab for recurrent conjunctival melanoma. JAMA Ophthalmol 2017;135:891–892.
27. Pinto Torres S, André T, Gouveia E, Costa L, Passos MJ. Systemic treatment of metastatic conjunctival melanoma. Case Rep Oncol Med 2017;2017:4623964.
28. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723.
29. Chaves LJ, Huth B, Augsburger JJ, Correa ZM. Eye-sparing treatment for diffuse invasive conjunctival melanoma. Ocul Oncol Pathol 2018;4:261–266.
30. Kazandjian D, Suzman DL, Blumenthal G, Mushti S, He K, Libeg M, et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist 2016;21:634–642.
31. Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 2018;19:1480–1492.
32. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521–2532.