Immune checkpoint inhibition and emerging immunotherapies in sinonasal mucosal melanoma
Year: 2025
Type: article
Abstract: Sinonasal mucosal melanoma (SNMM) is a rare but aggressive malignancy (comprising ~1-5% of all melanomas) with a markedly poorer prognosis than cutaneous melanoma. Historically, five-year survival for SNMM was around 20-30% due to high rates of local recurrence and distant metastasis despite aggressive surgery and radiation. The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, has begun to improve outcomes in SNMM. This scoping review summarizes the current evidence and emerging strategies for immunotherapy in SNMM. A comprehensive literature search (2015-2024) was conducted for studies on SNMM immunotherapy, including clinical trials, retrospective series, and case reports, given the rarity of this disease. SNMM has distinct biological features (lower tumor mutational burden, frequent NRAS and KIT mutations, rare BRAF mutations, and an “immune-cold” tumor microenvironment with low PD-L1 expression) that make it less responsive to ICIs compared to cutaneous melanoma. Anti-PD-1 monotherapy (e.g. nivolumab or pembrolizumab) produces objective response rates of ~15-25% in SNMM, with some durable remissions, while combined PD-1 plus CTLA-4 blockade roughly doubles the response rate (~30-40%) at the cost of significantly increased immune-related toxicity. Incorporating ICIs into multidisciplinary management has led to improved survival: recent multicenter series report 5-year overall survival approaching 40-45% in the immunotherapy era. In the adjuvant setting, PD-1 inhibitors are now often recommended after surgical resection of SNMM, showing prolonged recurrence-free survival in high-risk patients compared to historical interferon-based therapy. Neoadjuvant immunotherapy is an emerging approach for locally advanced SNMM, with early studies demonstrating tumor downstaging and pathologic responses in ~20-30% of patients, potentially translating into better long-term control. Novel combination strategies are under investigation, including ICIs paired with targeted therapies (such as anti-VEGF agents), aiming to overcome the immunosuppressive tumor microenvironment and enhance response rates. Immune checkpoint inhibition has become a critical component of SNMM treatment, contributing to meaningful improvements in survival and durable disease control for a subset of patients. However, SNMM remains less responsive to immunotherapy than its cutaneous counterpart, and a large proportion of patients still experience disease progression. Ongoing clinical trials and emerging immunotherapeutic approaches (perioperative immunotherapy, combination regimens, and adoptive cell therapies) hold promise for further improving outcomes. Future efforts are focused on optimizing immunotherapy sequencing, mitigating toxicity (particularly with combination regimens), and identifying predictive biomarkers to better select SNMM patients who are most likely to benefit from immunotherapeutic interventions.
Source: Otorhinolaryngology
Authors: Alexandria HARRIS, Matt LECHNER, Nyall R. LONDON Jr. Jr., Antoine MOYA-PLANA, Shirley Y. SU, Edward C. KUAN, Diana M. BELL, Carl H. SNYDERMAN, Eric W. WANG, Garret CHOBY
Institutions: University of Pittsburgh, University College London, Johns Hopkins University, Johns Hopkins Medicine, Institut Gustave Roussy, The University of Texas MD Anderson Cancer Center, University of California, Irvine, University of California, Irvine Medical Center, University of Pittsburgh Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4416455618