A neoadjuvant and adjuvant regimen of anti–PD-1 therapy with nivolumab and anti–LAG-3 therapy with relatlimab led to a 4-year event-free survival rate of 80% in patients with advanced, resectable melanoma, according to long-term findings from a phase II study published in the Journal of Clinical Oncology. Furthermore, 95% of patients who achieved a major pathologic response were event free at 4 years.
“If immunotherapy eliminates most of the tumor before surgery, then we have sufficiently trained the immune system for an antitumor response, which minimizes the possibility of recurrence,” said corresponding author Elizabeth Burton, PhD, Executive Director of The University of Texas MD Anderson Cancer Center’s Strategic Research Initiative Development (STRIDE) Program. “We are encouraged by these results showing the long-term benefit of this combination and approach for our patients and the opportunity it provides to learn as much as possible about what is driving this response to treatment.”
Study Methods and Rationale
Relatlimab was approved by the U.S. Food and Drug Administration in 2022 in combination with nivolumab for patients with advanced melanoma based on the results of the phase II/III RELATIVITY-047 trial.
Study authors then conducted this phase II trial to determine if the combination was safe and effective in the neoadjuvant setting for earlier-stage melanoma. The study was led by Rodabe Amaria, MD, Professor of Melanoma Medical Oncology at MD Anderson. Earlier findings confirmed the safety and efficacy of the regimen in this setting in 30 patients with stage III/IV surgically resectable melanoma.
After a median follow-up of 47 months, the study authors assessed long-term outcomes and predictive biomarkers.
Key Study Findings
At the time of the long-term analysis, 87% of the participating patients were still alive and 80% were still disease free.
The study authors found baseline upregulation of immune modulatory pathways that were associated with major pathologic responses. Patients who demonstrated high pretreatment levels of TIGIT were more likely to remain recurrence free. On the other hand, those who had high pretreatment levels of B7-H3 were more likely to experience recurrence. The researchers hope to further validate these biomarkers going forward.
“This study highlights the tremendous impact integrating excellent multidisciplinary care with team science can have on improving patient outcomes while advancing science and innovation. The neoadjuvant treatment approach allows us to quickly evaluate the clinical impact of a treatment and serves as a springboard for biomarker research,” Dr. Burton said. “This is a good starting point for where researchers can look in terms of mechanisms of resistance that could be potential therapeutic targets in the future.”
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
