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In recent years, the introduction and Federal Drug Administration approval of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for patients with advanced melanoma. These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has led to durable complete and partial responses in a large number of patients.
Additional checkpoint therapies, such as relatlimab, an Anti-Lymphocyte-activation gene 3 (LAG-3) antibodies (lymphocyte-Activation Gene 3), and other promising combinations, are on the horizon.
Clinical benefit from Immune Checkpoint Inhibitors (ICIs) is unpredictable; 25%–40% of patients experience recurrence.
Immun checkpoint inhibitors (ICIs) today form the first-line therapy for advanced melanoma, remarkably improving patient survival rates. However, primary/acquired resistances and immune-mediated adverse events (irAEs) remain significant challenges.
Anti-CTLA4 and Anti-PD-1 antibodies have significantly improved cancer management, especially in advanced melanoma, achieving tumor regression and long-term control in nearly 50% of patients. The combined Anti-CTLA4 and Anti-PD-1 therapy shows the highest 5-year survival rates in advanced melanoma and is effective in treating melanoma brain metastases.
Immune checkpoint inhibitor therapy achieves durable remissions in 30-50% of patients with metastatic melanoma.
Pembrolizumab and nivolumab are both anti-program death 1 (PD-1) antibodies. They have demonstrated remarkable efficacy when used alone. Additionally, nivolumab has shown significant effectiveness when combined with ipilimumab, with higher response rates, greater tumor shrinkage, and longer progression-free survival than either monotherapy alone.
A phase 3 study shows that adding an Anti-LAG3 antibody to Nivolumab improves progression-free survival, although the impact on overall survival is unclear
Resistance to immunotherapy can be overcome using fecal microbiota transplantation for patients with metastatic melanoma
Meta-analyses identified taxa like Eubacterium, Ruminococcus, Firmicutes, and Clostridium linked to recurrence. Recurrence prediction was strongest when validation cohort GMB (pretreatment gut microbiome) profiles matched the discovery cohort. For individuals with Jensen-Shannon divergence (JSD) ≤ 0.11, the AUC for recurrence prediction was 0.78 to 0.94 across regions. GMB composition remained stable after treatment.mGut bacterial markers may predict recurrence post-adjuvant ICB treatment in melanoma.
Patients who received Immune Checkpoint Inhibitors (ICIs) and those who had multimorbidity had significantly higher average total healthcare expenditures compared with Immune Checkpoint Inhibitors (ICIs) nonusers and no multimorbidity. In the fully adjusted model using Immune Checkpoint Inhibitors (ICIs)–multimorbidity interaction, no excess cost was added by multimorbidity. Use of Immune Checkpoint Inhibitors (ICIs), regardless of multimorbidity, is associated with increased healthcare expenditures.
see also:
Cancer immunotherapy / Immuno-Oncology & Melanoma (cutaneous)
Gut microbiota & Immune Checkpoint Inhibitors (ICIs)
Melanoma (cutaneous) & Drugs/Treatments