Treatment Outcomes of Mucosal Melanoma of Head and Neck: Efficacy of Immune Checkpoint Inhibitors for Advanced Disease

Overview

Journal Front Surg

Specialty General Surgery

Date 2023 Apr 21

PMID 37082097

Authors

Shusuke Ohshima

Yushi Ueki

Yusuke Yokoyama

Takeshi Takahashi

Ryusuke Shodo

Keisuke Yamazaki

Ryuichi Okabe

Hiroshi Matsuyama

Takafumi Togashi

Sumiko Takatsuka

Tatsuya Takenouchi

Arata Horii

Affiliations

Soon will be listed here.

Abstract

Background: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM.

Methods: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated.

Results: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period.

Conclusions: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

Citing Articles

Advances in immunotherapy for mucosal melanoma: harnessing immune checkpoint inhibitors for improved treatment outcomes.

Shan Z, Liu F Front Immunol. 2024; 15:1441410.

PMID: 39234260 PMC: 11373357. DOI: 10.3389/fimmu.2024.1441410.

References

Martini D, Hamieh L, McKay R, Harshman L, Brandao R, Norton C . Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events. Cancer Immunol Res. 2018; 6(4):402-408. DOI: 10.1158/2326-6066.CIR-17-0220. View

Munoz-Couselo E, Adelantado E, Ortiz C, Soberino Garcia J, Perez-Garcia J . -mutant melanoma: current challenges and future prospect. Onco Targets Ther. 2017; 10:3941-3947. PMC: 5558581. DOI: 10.2147/OTT.S117121. View

Schmidt M, David J, Yoshida E, Scher K, Mita A, Shiao S . Predictors of survival in head and neck mucosal melanoma. Oral Oncol. 2017; 73:36-42. DOI: 10.1016/j.oraloncology.2017.08.002. View

DAngelo S, Larkin J, Sosman J, Lebbe C, Brady B, Neyns B . Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis. J Clin Oncol. 2017; 35(2):226-235. PMC: 5559888. DOI: 10.1200/JCO.2016.67.9258. View

Ogata D, Haydu L, Glitza I, Patel S, Tawbi H, McQuade J . The efficacy of anti-programmed cell death protein 1 therapy among patients with metastatic acral and metastatic mucosal melanoma. Cancer Med. 2021; 10(7):2293-2299. PMC: 7982611. DOI: 10.1002/cam4.3781. View

Komiya K, Nakamura T, Abe T, Ogusu S, Nakashima C, Takahashi K . Discontinuation due to immune-related adverse events is a possible predictive factor for immune checkpoint inhibitors in patients with non-small cell lung cancer. Thorac Cancer. 2019; 10(9):1798-1804. PMC: 6718019. DOI: 10.1111/1759-7714.13149. View

Cinotti E, Labeille B, Cambazard F, Perrot J . Confocal Microscopy for Special Sites and Special Uses. Dermatol Clin. 2016; 34(4):477-485. DOI: 10.1016/j.det.2016.05.010. View

Matsuo M, Yasumatsu R, Masuda M, Toh S, Wakasaki T, Hashimoto K . Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. Oral Oncol. 2019; 101:104525. DOI: 10.1016/j.oraloncology.2019.104525. View

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

10.

Jethanamest D, Vila P, Sikora A, Morris L . Predictors of survival in mucosal melanoma of the head and neck. Ann Surg Oncol. 2011; 18(10):2748-56. PMC: 3155852. DOI: 10.1245/s10434-011-1685-4. View

11.

Al-Haseni A, Vrable A, Qureshi M, Mathews S, Pollock S, Truong M . Survival outcomes of mucosal melanoma in the USA. Future Oncol. 2019; 15(34):3977-3986. DOI: 10.2217/fon-2019-0465. View

12.

Long G, Stroyakovskiy D, Gogas H, Levchenko E, De Braud F, Larkin J . Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015; 386(9992):444-51. DOI: 10.1016/S0140-6736(15)60898-4. View

13.

Robert C, Long G, Brady B, Dutriaux C, Maio M, Mortier L . Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2014; 372(4):320-30. DOI: 10.1056/NEJMoa1412082. View

14.

Koto M, Demizu Y, Saitoh J, Suefuji H, Tsuji H, Okimoto T . Multicenter Study of Carbon-Ion Radiation Therapy for Mucosal Melanoma of the Head and Neck: Subanalysis of the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) Study (1402 HN). Int J Radiat Oncol Biol Phys. 2017; 97(5):1054-1060. DOI: 10.1016/j.ijrobp.2016.12.028. View

15.

Lopez F, Rodrigo J, Cardesa A, Triantafyllou A, Devaney K, Mendenhall W . Update on primary head and neck mucosal melanoma. Head Neck. 2014; 38(1):147-55. PMC: 4986507. DOI: 10.1002/hed.23872. View

16.

Chi Z, Li S, Sheng X, Si L, Cui C, Han M . Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases. BMC Cancer. 2011; 11:85. PMC: 3056833. DOI: 10.1186/1471-2407-11-85. View

17.

Li J, Kan H, Zhao L, Sun Z, Bai C . Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review. Ther Adv Med Oncol. 2020; 12:1758835920922028. PMC: 7238311. DOI: 10.1177/1758835920922028. View

18.

Weber J, Mandala M, Del Vecchio M, Gogas H, Arance A, Cowey C . Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017; 377(19):1824-1835. DOI: 10.1056/NEJMoa1709030. View

19.

Tomizuka T, Namikawa K, Higashi T . Characteristics of melanoma in Japan: a nationwide registry analysis 2011-2013. Melanoma Res. 2017; 27(5):492-497. DOI: 10.1097/CMR.0000000000000375. View

20.

de Giorgi V, Sestini S, Bruscino N, Janowska A, Grazzini M, Rossari S . Prevalence and distribution of solitary oral pigmented lesions: a prospective study. J Eur Acad Dermatol Venereol. 2009; 23(11):1320-3. DOI: 10.1111/j.1468-3083.2009.03186.x. View