Relatlimab/nivolumab combo improves melanoma outcomes, may avoid surgery


Findings from a study of patients with stage III melanoma treated with a combination of the immune checkpoint inhibitors relatlimab and nivolumab before surgery showed that the adjuvant therapy was safe and completely cleared all viable tumours in 57% of the patients.

These results were published in Nature.

A total of 30 patients with resectable clinical stage III or oligometastatic stage IV melanoma were included. The participating patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every four weeks) followed by surgery, and then 10 doses of adjuvant combination therapy.

In addition to meeting the primary endpoint of complete clearance, the overall pathologic response rate (up to 50% of viable tumours left at the time of surgery) was 70%. No patients had grade 3 or 4 immune-related adverse events (IRAEs) in the neoadjuvant (pre-surgery) setting or confirmed toxicity-related surgical delays. One patient developed a brain metastasis during neoadjuvant therapy and did not proceed to surgery.

“With clinical stage III melanoma, the risk that the cancer comes back after surgery can be as high as 50 per cent,” said lead/corresponding author Dr. Rodabe Amaria, associate professor of Melanoma Medical Oncology, in a press release. “One of the goals of neoadjuvant immunotherapy is to reduce the chance of recurrence by evaluating treatments in earlier stage, operable disease that have been successful for stage IV melanoma.”

“Our findings support the combination of relatlimab and nivolumab as a safe and effective treatment option in the neoadjuvant setting for stage III melanoma.”

After a median of 24.4 months follow-up in the 29 patients who underwent surgery, the rate of recurrence-free survival (RFS) was 97% at one year and 82% at two years. RFS rates were highest in patients with complete clearance at one year and 91% at two years, compared to 92% and 69% in patients without complete clearance before surgery. The one- and two-year overall survival rates for all patients were 93% and 88%, respectively.

In the release, the authors note that their results are favourable compared to two prior study arms, which assessed nivolumab either alone or in combination with the CTLA-4 checkpoint inhibitor ipilimumab. Those results, reported by Dr. Amaria and her colleagues in Nature Medicine in 2018, showed a complete clearance rate before surgery of 45%, with 73% of patients experiencing grade 3 side effects in the combination arm. The nivolumab monotherapy arm achieved a complete clearance rate of 25%, with 8% of patients experiencing grade 3 side effects. The high toxicity rate led to the early closure of the previous study.

“We’re very pleased to see that the combination of relatlimab and nivolumab balanced safety and efficacy, and it did not result in any delays to surgery,” Dr. Amaria said. “We want to provide patients with a treatment option that will help reduce the risk of their cancer returning after surgery. Our data complement the RELATIVITY-047 study results and provide further evidence to support the use of this combination in melanoma.”

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