Figure 3.

Subsequent line treatment algorithm for unresectable or metastatic cutaneous melanoma. *There are no data to guide treatment for progression on first-line nivolumab plus relatlimab. Referral for clinical trial is preferred in this scenario. †The decision to continue ICI therapy beyond initial radiographic progression should be based on melanoma-associated symptoms, disease kinetics, and the presence or absence of irAEs. ‡Progression of disease on BRAF/MEK inhibition that may worsen with removal of targeted therapy is one specific circumstance in which this Expert Panel would consider the use of triplet therapy. §Primary resistance is defined as: best response of PD or SD for <6 months following at least 6 weeks of drug exposure. Secondary resistance is defined as: CR, PR, or SD for >6 months following at least 6 weeks of drug exposure.139 ¶ Ipilimumab monotherapy and ipilimumab plus pembrolizumab are other regimens that have demonstrated some efficacy for patients with advanced melanoma that has progressed on anti-PD1 therapy. BRAF/MEK inhibition could be considered as well in patients with BRAFV600-mutated disease in need of rapid response. CNS, central nervous system; CR, complete response; CTLA-4, cytotoxic T lymphocyte antigen-4; ICI, immune checkpoint inhibitor; irAEs, immune-related adverse events; LDH, lactate dehydrogenase; NED, no evidence of disease; NGS, next generation sequencing; OS, overall survival; PD, progressive disease; PD-1, programmed cell death protein 1; PR, partial response; SD, stable disease.