Approach to selecting initial systemic therapy in patients with extracranial metastatic cutaneous melanoma

LDH: lactate dehydrogenase; AJCC: American Joint Committee on Cancer; PFS: progression-free survival.

* Eligibility for immunotherapy is influenced by patient performance status, medical comorbidities, history of autoimmune disease, and use of immunosuppressive therapy, including glucocorticoids. Refer to UpToDate content on systemic treatment of metastatic melanoma with molecular alterations.

¶ The presence of brain (ie, intracranial) metastases also signals aggressive disease. However, management of patients with brain metastases is complex and may also involve other treatment strategies. Refer to UpToDate content on management of brain metastases in melanoma.

Δ In patients with BRAF V600 mutant melanoma, we recommend combination immunotherapy with nivolumab plus ipilimumab over combination targeted therapy with BRAF plus MEK inhibitors as this approach improves overall survival and offers a greater opportunity for long-term treatment-free survival. For those unlikely to tolerate nivolumab plus ipilimumab (eg, older adults, patients with a history of autoimmune disease), the combination of nivolumab-relatlimab is an appropriate alternative and is preferred over single-agent immunotherapy.

◊ Single-agent immunotherapy is an option for patients who are anticipated to not tolerate the potential toxicities of combination immunotherapy. In patients with pre-existing autoimmune disease, limited data suggest that most can safely receive checkpoint inhibitor immunotherapy, but may be at higher risk for specific irAEs or exacerbation of their underlying autoimmune disorders. Refer to UpToDate content on toxicities associated with immunotherapy.

§ All combinations are reasonable options. While not compared directly, all appear to have similar efficacy. Selection is based on sites of metastatic disease, patient convenience, and potential toxicities. Refer to UpToDate content on systemic treatment of metastatic melanoma with molecular alterations.