What are the indications for immunotherapy in malignant melanoma (cancer)?

From the Guidelines

Immunotherapy is indicated for melanoma patients with advanced disease, including metastatic (stage IV) or unresectable stage III melanoma, and as adjuvant therapy for patients with completely resected stage III or IV melanoma who have a high risk of recurrence, as supported by the most recent guidelines from 2019 1. The primary immunotherapy agents used are immune checkpoint inhibitors such as pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).

• For metastatic disease, anti-PD-1 therapies like pembrolizumab or nivolumab are typically given as first-line treatment, either as monotherapy or in combination with ipilimumab (anti-CTLA-4) for more aggressive cases.
• Standard dosing for pembrolizumab is 200 mg IV every 3 weeks or 400 mg every 6 weeks, while nivolumab is given at 240 mg every 2 weeks or 480 mg every 4 weeks.
• For adjuvant therapy after complete surgical resection, treatment typically continues for up to one year. Immunotherapy works by removing the brakes on the immune system, allowing T cells to recognize and attack melanoma cells.
• Treatment selection should consider the patient's performance status, comorbidities, and BRAF mutation status, as patients with BRAF mutations may be candidates for targeted therapy instead of or in addition to immunotherapy, as discussed in the 2020 ESMO consensus conference recommendations 1.
• Immune-related adverse events must be monitored closely, as these treatments can cause significant autoimmune complications requiring prompt intervention, with a higher risk of serious immune-mediated toxicities associated with combination therapy, as noted in the 2016 NCCN guidelines insights 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Unresectable or Metastatic Melanoma YERVOY, as a single agent or in combination with nivolumab, is indicated for the treatment of unresectable or metastatic melanoma in adult and pediatric patients 12 years and older.

1 INDICATIONS AND USAGE

1.1 Unresectable or Metastatic Melanoma OPDIVO, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

INDICATIONS AND USAGE KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated: Melanoma for the treatment of patients with unresectable or metastatic melanoma.

The indication for immunotherapy in melanomas is for the treatment of unresectable or metastatic melanoma in adult and pediatric patients 12 years and older.

• Ipilimumab and nivolumab can be used as single agents or in combination for this indication.
• Pembrolizumab is also indicated for the treatment of patients with unresectable or metastatic melanoma. Key points to consider:
• Age: 12 years and older
• Type of melanoma: unresectable or metastatic
• Treatment options: ipilimumab, nivolumab, pembrolizumab, as single agents or in combination 2, 3, 4

From the Research

Indications for Immunotherapy in Melanomas

• Immunotherapy with checkpoint inhibitors may be offered to BRAF-mutated and wild-type patients and is associated with longer and durable responses that can continue over years 5.
• Combination immune checkpoint inhibitor therapy with ipilimumab and nivolumab in untreated, metastatic melanoma has achieved a ten-year melanoma-specific survival of 52% 6.
• 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 7.
• Immunotherapy with checkpoint inhibitors has revolutionised the outcomes for melanoma patients, with significant improvements in relapse-free survival and distant metastasis-free survival in patients with resected high-risk stage III disease and stage IIB/C disease 8.

Patient Selection for Immunotherapy

• Patients with BRAF V600-mutant advanced melanoma may benefit from first-line pembrolizumab treatment, with a longer overall survival compared to first-line dabrafenib/trametinib treatment 7.
• Patients with metastatic melanoma who have primary resistance or develop secondary resistance to anti-PD-1 therapy may benefit from alternative treatment options, such as targeted BRAF/MEK inhibition or personalized, autologous tumor-infiltrating lymphocyte therapy 6.
• Patients at high risk for immune-related adverse events may still be considered for immunotherapy with checkpoint inhibitors, with modified immunosuppression in patients with autoimmune disease or previous organ transplantation 6.

Ongoing Research and Future Directions

• Ongoing registration phase III trials are currently evaluating newer immunotherapy combinations and the role of BRAF/MEK-directed targeted therapy for stage II melanoma 8.
• There is a critical need to evaluate the use of tissue and blood-based biomarkers to better select patients who will recur and avoid unnecessary treatment for the majority of patients cured by surgery alone 8.
• Emerging therapeutics, such as novel engineered oncolytic viral and human leukocyte antigen (HLA)-restricted immune-mediated T-cell therapies, show promising clinical benefit in ongoing clinical trials 6.