Multinational real-world study of combination immunotherapy sequences in metastatic melanoma

Immune checkpoint inhibitors (ICIs) demonstrated significant efficacy in metastatic melanoma treatment. However, there is a lack of robust data to determine the optimal sequencing of these therapies for individual patients. In particular, the role of relatlimab+nivolumab (rela/nivo) within treatment sequences remains poorly defined. Choosing the optimal sequence is important, as an inapproprate order may compromise the effectiveness of subsequent treatments. A multinational study evaluated 190 metastatic melanoma patients across three treatment arms: rela/nivo followed by ipilimumab-nivolumab (ipi/nivo) (arm A; n=40); ipi/nivo followed by rela/nivo (arm B, n=71); and anti-PD-1 followed by rela/nivo (arm C; n=79). The overall response rate to second treatment was highers in arm C (30.4%), followed by arm B (28.1%) and arm A (17.5%). Patients with secondary resistance to first-treatment ICIs had better responses to second-treatment ICIs than those with primary resistance, particularly in arm B. Median overall survival from date of first ICI treatment was significantly longer in arms B (40.9 months) and C (42.5 months) compared with arm A (16.3 months). The authors conclude that these findings suggest that rela/nivo may remain active following anti-PD-1 or ipi/nivo therapy, and that sequencing ipi/nivo before rela/nivo may yield better outcomes than starting with rela/nivo.