Investigative Treatments for Metastatic Melanoma

EP: 1.Patient Case: A 62-Year-Old Female with Stage IV BRAF-Mutated Melanoma

EP: 2.Prognosis and Diagnosis of Advanced Melanoma

EP: 3.Treatment Options for Metastatic Melanoma

EP: 4.First-Line and Sequencing Treatment Decisions

EP: 5.Treating Stage IV BRAF-Mutated Melanoma

EP: 6.Managing Immune-Related Adverse Events

EP: 7.Second-Line Treatments for Metastatic Melanoma

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EP: 8.Investigative Treatments for Metastatic Melanoma

Case: A 62-Year-Old Female with Stage IV Melanoma

• A 62-year-old female consulted with her dermatologist for removal of a pigmented lesion that had recently become darker.
  • She noted that she had been experiencing persistent fatigue, shortness of breath, and a dry cough that she attributed to a prior COVID-19 infection.
  • LDH: 174 UI/L
• Excisional biopsy reveals melanoma with a Breslow depth of 1.2 mm, ulcerated, mitotic rate 4/mm2
  • The patient underwent wide local excision and sentinel node mapping
  • Staining was positive for melanoma in the right axillary node
  • CT of the chest, abdomen, and pelvis indicated multiple lesions in both lungs
  • The patient underwent core-needle biopsy of the largest lung lesion, measuring 1 cm
  • Pathology revealed metastatic melanoma, cutaneous nonacral with a positive BRAF V600E mutation
  • ECOG PS 1
• Diagnosis: Stage IV Melanoma, T2b N1a M1b

This is a video synopsis/summary of a Case-Based Peer Perspective, featuring Michael B. Atkins, MD.

Although treatment of metastatic BRAF-mutant melanoma has improved dramatically with combination immunotherapy and targeted therapies, key unmet needs remain. Patients with symptomatic brain metastases are challenged to treat with immunosuppressive therapies. Those with BRAF wild-type disease resistant to immunotherapies lack effective treatments.

However, there are various promising approaches emerging from recent trials: Tumor-infiltrating lymphocyte therapy has shown 30% to 40% response rates with durability in resistant disease; immunotherapy triplet combinations, such as nivolumab plus ipilimumab plus relatlimab, may improve efficacy without added toxicity; Treg-depleting CTLA-4 antibodies and Treg-degrading treatments have demonstrated reduced immunosuppression; T-cell engagers targeting brain metastases have demonstrated early activity; and engineered cytokines and intralesional therapies have displayed promising results.

As these agents are investigated further, referring patients with resistant disease for clinical trials helps advance the field and may benefit these patients out of therapeutic options.

Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.