What is the best immunotherapy for melanoma?

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Last updated: June 30, 2025View editorial policy

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From the Guidelines

The best immunotherapy for melanoma currently is the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), which has shown superior efficacy compared to single-agent treatments. This regimen typically involves nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks as maintenance therapy 1. For patients who cannot tolerate the combination due to side effects, single-agent PD-1 inhibitors like pembrolizumab (Keytruda) at 200 mg every 3 weeks or nivolumab at 240 mg every 2 weeks are effective alternatives.

  • Key considerations for selecting the best immunotherapy for melanoma include:
    • The presence of BRAF mutations, which may influence the choice between targeted therapy and immunotherapy 1
    • The patient's overall health, medical history, and ability to tolerate potential side effects 1
    • The potential for durable disease control and long-term survival with immunotherapy 1
  • Treatment is typically continued for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Patients should be monitored for immune-related adverse events including colitis, pneumonitis, hepatitis, endocrinopathies, and skin reactions, which may require prompt intervention with corticosteroids and temporary or permanent discontinuation of therapy 1.

From the FDA Drug Label

CHECKMATE-067 demonstrated statistically significant improvements in OS and PFS for patients randomized to either OPDIVO-containing arm as compared with the ipilimumab arm. CHECKMATE-76K demonstrated a statistically significant improvement in RFS for patients randomized to the OPDIVO arm compared with the placebo arm. CHECKMATE-238 demonstrated a statistically significant improvement in RFS for patients randomized to the OPDIVO arm compared with the ipilimumab 10 mg/kg arm.

The best immunotherapy for melanoma is nivolumab (OPDIVO), as it has shown statistically significant improvements in overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) in several clinical trials, including CHECKMATE-067, CHECKMATE-76K, and CHECKMATE-238 2 2.

  • Key benefits of nivolumab include:
    • Improved OS and PFS compared to ipilimumab
    • Improved RFS compared to placebo
    • Statistically significant improvements in clinical trials
  • Important considerations: nivolumab may have different efficacy and safety profiles compared to other immunotherapies, and treatment decisions should be made on a case-by-case basis.

From the Research

Immunotherapy Options for Melanoma

  • The best immunotherapy for melanoma depends on various factors, including the patient's BRAF mutation status and overall health 3, 4.
  • Combination ipilimumab/nivolumab (ipi/nivo) has shown improved progression-free survival (PFS) and overall survival (OS) compared to anti-PD-1 monotherapy in patients with BRAF wild-type (WT) melanoma 4.
  • In patients with BRAF V600-mutant melanoma, sequential immunotherapy and targeted therapy have been shown to provide clinically meaningful survival benefits 3.
  • Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have become standards of care in metastatic melanoma, with comparable efficacy and toxicity profiles 5.

Treatment Considerations

  • The choice of treatment should be based on the patient's individual needs and preferences, as well as the clinician's expertise 5.
  • Combination therapy with ipi/nivo may be considered for patients with BRAF WT melanoma, while sequential immunotherapy and targeted therapy may be suitable for patients with BRAF V600-mutant melanoma 3, 4.
  • Patients should be closely monitored for immune-related adverse events (irAEs), which can occur with immunotherapy treatment 6, 7.

Efficacy and Safety

  • Nivolumab and pembrolizumab have been shown to have comparable efficacy and safety profiles in advanced melanoma treatment 5.
  • Combination ipilimumab/nivolumab has been associated with improved PFS and OS in patients with BRAF WT melanoma, but may also increase the risk of irAEs 4.
  • Sequential immunotherapy and targeted therapy have been shown to provide clinically meaningful survival benefits in patients with BRAF V600-mutant melanoma, with a manageable safety profile 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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