Most patients with advanced melanoma remain disease-free four years after pre-surgical immunotherapy

Elizabeth Burton, PhD. Photo courtesy The University of Texas MD Anderson Cancer Center

In a significant advance for the management of advanced melanoma, a Phase II clinical trial conducted at The University of Texas MD Anderson Cancer Center in Houston has demonstrated that the majority of patients with stage III resectable melanoma who received pre-surgical immunotherapy remain alive and disease-free four years after treatment.

The study, published in the Journal of Clinical Oncology, followed 30 patients treated with a combination of two immune checkpoint inhibitors: nivolumab (anti-PD-1) and relatlimab (anti-LAG-3). The results showed that 87% of patients were alive and 80% had no recurrence of their cancer at the four-year mark. Among those who achieved a major pathologic response—defined as substantial tumour regression at the time of surgery—the recurrence-free rate was even higher, at 95%.

“If immunotherapy eliminates most of the tumour before surgery, then we have sufficiently trained the immune system for an antitumour response, which minimizes the possibility of recurrence,” Elizabeth Burton, PhD, said in a press release. “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.” She is executive director of MD Anderson’s Strategic Research Initiative Development (STRIDE) program.

Stage III melanoma is associated with a high risk of recurrence following surgery, prompting interest in neoadjuvant (pre-surgical) immunotherapy to shrink tumours and prime the immune system against future relapse. Relatlimab, a LAG-3 inhibitor, was approved by the U.S. FDA in 2022 for use with nivolumab in advanced melanoma, based on the RELATIVITY-047 trial. The current study, led by Dr. Rodabe Amaria, professor of Melanoma Medical Oncology, is the first to evaluate this combination in earlier-stage disease using a neoadjuvant approach.

Researchers also identified biomarkers that may predict which patients are most likely to benefit from this approach. High pre-treatment levels of TIGIT or low levels of B7-H3 were associated with the greatest likelihood of remaining recurrence-free. “This study highlights the tremendous impact integrating excellent multi-disciplinary care with team science can have on improving patient outcomes while advancing science and innovation,” Dr. Burton said. “The neoadjuvant treatment approach allows us to quickly evaluate the clinical impact of a treatment and serves as a springboard for biomarker research.”

The team is collaborating with MD Anderson’s James P. Allison Institute to validate these biomarkers and further investigate their role in the tumour microenvironment. The trial was funded by Bristol Myers Squibb and supported by MD Anderson’s Moon Shots Program and the U.S. National Cancer Institute.