Long-term survival achieved in stage III melanoma with pre-surgery immunotherapy

Four years after pre-surgery treatment with a novel combination of immune checkpoint inhibitors, nivolumab and relatlimab, 87% of patients with stage III melanoma remained alive, according to new results from a study led by researchers at The University of Texas MD Anderson Cancer Center.

Long-term follow-up data from this Phase II study, published today in the Journal of Clinical Oncology, demonstrate this combination provides long-term benefits to patients when given before and after surgery, and identified unique biomarkers associated with better outcomes and lower chance of recurrence.

Of the 30 patients enrolled on the study, 80% had no recurrence of their cancer after four years. For patients who had a significant response, called a major pathologic response, from treatment when evaluated at the time of surgery, even more remained recurrence free, at 95%.

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. 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."

Elizabeth Burton, Ph.D., corresponding author, executive director of MD Anderson's Strategic Research Initiative Development (STRIDE) program

Stage III melanoma has a high risk of recurrence following surgery, highlighting an opportunity for the addition of pre-surgical, or neoadjuvant, immunotherapy to shrink the tumor and prime the immune system to guard against future recurrences.

Relatlimab is a LAG-3 inhibitor, an immune checkpoint inhibitor that was approved in 2022 in combination with nivolumab by the Food and Drug Administration (FDA) for patients with advanced melanoma based on the Phase II/III RELATIVITY-047 clinical trial, led by Hussein Tawbi, M.D., Ph.D., professor of Melanoma Medical Oncology.

In this Phase II trial, led by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology, researchers were first to evaluate this combination in the neoadjuvant setting for earlier stage disease. Initial findings reported this combination was safe and effective in that setting.

Because of the strong association to outcomes with major pathologic response, researchers evaluated biomarkers to better understand the factors associated with treatment response.

They found that patients who had high pre-treatment levels of one biomarker, called TIGIT, or low levels of another biomarker, called B7-H3, had the best chance of remaining recurrence-free, highlighting the potential to use these markers to predict patient responses in the future.

"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. The neoadjuvant treatment approach allows us to quickly evaluate the clinical impact of a treatment and serves as a springboard for biomarker research." 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."

Going forward, the authors are collaborating with researchers at MD Anderson's James P. Allison Institute to validate these biomarkers and to use spatial profiling to further understand where they are located and how they can impact the tumor microenvironment.

This clinical trial was funded by Bristol Myers Squibb, with additional support for this study by MD Anderson's Moon Shots Program, the National Cancer Institute (P50CA221703, P30 CA016672, UM1 TR004538, and P30 CA008748). Tawbi and Amaria were co-senior authors on this study, together with Jennifer Wargo, M.D., professor of Surgical Oncology.