Thinking beyond immunotherapy: implementing a multimodal care plan to facilitate extended survival in stage IV melanoma

The treatment of metastatic melanoma has been revolutionized with the introduction of immune checkpoint inhibitors, though approximately 50% of patients will progress at 12 months even with the most robust immunotherapy combinations. As these drugs are now first-line treatment for advanced melanoma, it is imperative to define the role and benefits of multimodal therapy adjunct to systemic therapy. This case describes a patient with v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutant stage IV melanoma who has been treated for over 9 years with a combination of systemic and local therapeutics: anti-Cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed cell death protein 1 receptor (PD1), and targeted therapies, stereotactic radiosurgery, and multiple metastasectomies. Through multidisciplinary care with the help of genomic analysis, this patent’s survival has been extended far past conventional estimates. Molecular profiling revealed an acquired NRAS mutation, which helped explain clinical findings and allowed for a more tailored therapeutic regimen. This report demonstrates that effective surgical resection of nonresponding or progressing lesions can lead to long-term survival even in patients with severe disease burden. Continuous clinical and molecular monitoring can also help shape patients’ treatment courses. The effectiveness of multimodal treatment, incorporating local therapies with molecular profiling in conjunction with systemic therapies, should be considered by interdisciplinary care teams to strive for durable survival in patients with historically grim prognoses.