From the Guidelines
Therapy for melanoma with lymph node involvement should prioritize adjuvant therapy with immune checkpoint inhibitors, such as nivolumab or pembrolizumab, for 12 months, due to improved recurrence-free survival, as recommended by the most recent guidelines 1. The primary treatment involves surgical excision of the primary tumor with wide margins and sentinel lymph node biopsy or complete lymph node dissection if metastasis is confirmed. Following surgery, adjuvant therapy is recommended, with the following options:
- For BRAF-mutated melanoma, targeted therapy with dabrafenib plus trametinib is an alternative option, as supported by evidence from the COMBI-AD trial 1.
- For BRAF wild-type melanoma, nivolumab or pembrolizumab are the preferred adjuvant therapy options, as recommended by the ASCO guideline update 1. Some key points to consider:
- Nivolumab and pembrolizumab are FDA-approved adjuvant treatments for patients with melanoma with lymph node involvement who have undergone complete disease resection.
- Patients with stage IIIA disease with <1 mm involvement in the sentinel lymph node have a relatively better prognosis and lower risk of relapse, and treatment should be individualized after discussing the risk-benefit quotient with these patients.
- Radiation therapy may be considered for patients with multiple positive nodes or extracapsular extension. Regular follow-up with physical examinations, imaging studies, and blood tests is essential for monitoring recurrence, as supported by the ESMO clinical practice guidelines 1. These treatments work by either directly removing cancerous tissue, enhancing the immune system's ability to recognize and attack cancer cells, or targeting specific mutations driving tumor growth, ultimately improving survival outcomes for patients with lymph node-positive melanoma, as demonstrated by the improved recurrence-free survival rates in the MK-3475 trial 1.
From the FDA Drug Label
YERVOY is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for: Melanoma • Treatment of unresectable or metastatic melanoma in adults and pediatric patients 12 years and older as a single agent or in combination with nivolumab. (1. 1) • Adjuvant treatment of adult patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy. (1.2)
Ipilimumab (YERVOY) is indicated for the treatment of melanoma, including:
- Unresectable or metastatic melanoma in adults and pediatric patients 12 years and older as a single agent or in combination with nivolumab.
- Adjuvant treatment of melanoma in adult patients with cutaneous melanoma and pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy 2.
From the Research
Therapy for Melanoma with Lymph Node Involvement
- The management of melanoma with lymph node involvement has evolved over time, with a focus on optimizing treatment outcomes while minimizing unnecessary procedures 3, 4.
- Sentinel lymph node (SLN) biopsy remains a crucial tool for lymph node staging in melanoma, providing important prognostic information and guiding treatment decisions 3, 4.
- Recent studies have shown that complete lymph node dissection may not be necessary for all patients with positive SLN, and that conservative management or adjuvant systemic immunotherapy may be effective alternatives 3, 4.
Treatment Options for BRAF-Mutant Melanoma
- Dabrafenib plus trametinib has been shown to be effective in the treatment of BRAF V600-mutated metastatic melanoma, with improved overall survival and response rates compared to single-agent BRAF inhibitors 5, 6, 7.
- Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma, based on longer overall survival and lower risk of immune evasion 5.
- Adjuvant dabrafenib and trametinib therapy has been shown to be effective in patients with resected BRAF-mutated melanoma, with a manageable toxicity profile and low incidence of treatment discontinuations 6.
Future Directions
- Further research is needed to determine the optimal treatment strategies for patients with melanoma and lymph node involvement, including the role of SLN biopsy and adjuvant systemic immunotherapy 3, 4.
- The development of novel prognostic and predictive biomarkers may help to personalize treatment approaches and improve outcomes for patients with melanoma 3.