In an extended follow-up of a phase II trial reported in the Journal of Clinical Oncology, Burton et al examined outcomes with neoadjuvant and adjuvant relatlimab-rmbw plus nivolumab in patients with resectable melanoma. Relatlimab targets LAG3, while nivolumab targets PD-1.
Study Details
In the study, 30 patients with stage III or IV disease enrolled at either The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center between September 2018 and September 2020 received nivolumab at 480 mg plus relatlimab at 160 mg every 4 weeks for 2 cycles before surgery, followed by up to 10 doses after surgery. A prior report from the trial showed achievement of major pathologic response (MPR; ≤ 10% viable tumor) in 63% of patients.
Key Findings
At updated analysis, median follow-up was 47 months (range = 8.2–67.8 months).
At 4 years from the start of neoadjuvant treatment, 80% of patients remained event-free, including 95% of patients who achieved MPR. Recurrence-free survival was 95% among patients with MPR and 60% among those with < MPR. Overall survival was 87%, including 95% among those with MPR and 80% among those with < MPR.
Longitudinal analysis of gene expression identified baseline upregulation of numerous immune modulatory pathways associated with achievement of MPR (eg, those involving B cells, CD45+ cells, CD8+ T cells, cytotoxic cells, natural killer cells, PD-1, TIGIT); however, increased B7-H3 expression was associated with resistance to the combination.
The investigators concluded: “This work demonstrates the long-term benefit of neoadjuvant nivolumab and relatlimab and identifies a potentially targetable predictor of resistance to this combination therapy.”
Elizabeth M. Burton, PhD, MBA, of the Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by BMS, grants from the National Cancer Society, and others. For full disclosures of all study authors, visit ascopubs.org.
