Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma
Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas.
We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016.
Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4–73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5–4.6] and 5 months (95% CI 2.6–33.1), respectively (p = 0.0147).
In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially.
KeywordsMucosal melanoma Immunotherapy Ipilimumab Pembrolizumab Anti-PD1 Anti-CTLA4
B-Raf proto-oncogene, serine/threonine kinase
Breast cancer 1
KIT proto-oncogene, receptor tyrosine kinase
Disease control rate
Duration of response
Immune response evaluation criteria in solid tumours
Immune-related response criteria
Methyl-CpG-binding domain 4
NRAS proto-oncogene, GTPase
Objective response rate
Splicing factor 3b subunit 1
Somatic nucleotide variants
Tumor growth rate
Tumour volume at baseline
Tumour volume at time t
AM-P, FJ, AMME, LD and CR conceptualized the manuscript, harmonized and edited the text and references and produced the figures. CR and IG performed statistical analysis. RGHG, SA, SR, J-YS and SV were responsible for data collection and analysis. All the authors contributed to the writing and editing of the manuscript. All the authors approved the final version.
No relevant funding.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The translational research study NCT02105168 was approved by the Institutional Review Board at Gustave Roussy Cancer Campus on April 7, 2014. All the methods and procedures associated with this study were conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
All the patients have given their written authorization to perform research on their tumour samples by signing the Institutional Tumor Bank form (before April 2014) or the form of the translational research study NCT02105168. All the patients provided written informed consent to the use of their anonymized data in scientific studies.
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