New Checkpoint Inhibitor Immunotherapy Treatment for Advanced Melanoma Shows Promise

Nancy Schroeder and her husband Mark

Nancy Schroeder, shown here with her husband, Mark, has participated in two important clinical trials at MSK.

When Nancy Schroeder found out her melanoma had spread to her lymph nodes four years after she’d had surgery from a local dermatologist near her home in Florida, she knew she needed to go to Memorial Sloan Kettering Cancer Center (MSK) to benefit from the latest research and newest therapies. During her first appointment at MSK, she learned about a clinical trial that was testing an experimental advanced melanoma immunotherapy given before surgery.

“I was thrilled to hear about the trial,” Nancy says. “To me, it made so much sense. I was excited to be able to participate.” Today, more than two years after completing her treatment, Nancy, now 70, has no signs of cancer.

Findings from the study, a phase 2 trial, were published October 26, 2022, in Nature. The paper reports that for certain patients with advanced (stage 3 or stage 4) melanoma, a combination of the immunotherapy drugs nivolumab (Opdivo®) and relatlimab (Opdualag™) given before surgery (called neoadjuvant treatment) prevented the disease from coming back. About two-thirds had a major response to the drugs. After an average of two years, most patients remain cancer free.

“The take-home message is that most patients responded really well to this drug combination,” says MSK melanoma surgeon Charlotte Ariyan, co-senior author of the paper. “Additionally, the side effects were markedly reduced compared with other types of immunotherapy. This meant that none of the patients in the trial had to delay their surgery after getting the first part of their treatment.”

Improving the Prognosis for Advanced Melanoma by Using Checkpoint Inhibitors That Target PD-1 and LAG-3

Nivolumab and relatlimab both belong to a class of immunotherapy drugs called checkpoint inhibitors. They help the body fight cancer by taking the brakes off the immune system, enabling it to recognize and attack cancer cells. Nivolumab targets a protein called PD-1; relatlimab targets a protein called LAG-3.

The take-home message is that most patients responded really well to this drug combination.
Charlotte E. Ariyan melanoma surgeon

At the time this trial was launched at MSK in 2019, relatlimab was still experimental. In March 2022, it received approval from the U.S. Food and Drug Administration for use in combination with nivolumab in patients whose metastatic melanoma could not be removed surgically.

MSK Patients Have Early Access to Cutting-Edge Therapies for Melanoma

“We opened this trial three years before relatlimab was approved,” says MSK medical oncologist and melanoma specialist Michael Postow, co-first author of the study. “We want patients to know that when they come to see us, they get access to new, promising treatments that are not available elsewhere.” This trial was conducted at only two hospitals, MSK and the University of Texas MD Anderson Cancer Center in Houston.

Clinical Trial Studies Neoadjuvant Checkpoint Inhibitors for Advanced Melanoma

The study enrolled a total of 30 patients who had advanced, aggressive melanoma (stage 3 or stage 4) that was surgically removable. The patients in the trial had two rounds of the immunotherapy combination, followed by surgery to remove their cancer. Twenty-nine of the 30 eventually had surgery.

The results were extremely encouraging. In 66% of patients who had surgery, the combination therapy killed most or all of the cells in the tumors — known as a major pathologic response. In a few additional patients, the tumors shrank — known as a partial response. After surgery, many of the patients had additional immunotherapy to increase the chances that all the cancer cells were destroyed.

We want patients to know that when they come to see us, they get access to new, promising treatments that are not available elsewhere.
Michael A. Postow medical oncologist and melanoma specialist

“This trial highlights the way we collaborate with each other,” Dr. Postow says. “The surgeons and medical oncologists really worked well together to determine which patients were most likely to benefit from this approach.”

When Dr. Postow and Dr. Ariyan saw Nancy, they knew she was a good candidate for the study, and Nancy understood the value of participating in clinical research.

Clinical Trials Advance Melanoma Treatment

The melanoma trial was not Nancy’s first at MSK. In 1997, she was diagnosed with breast cancer. She participated in the pivotal MSK-led trial that confirmed sentinel lymph node biopsies could help patients avoid more extensive surgeries. “I think it’s so important for patients to be informed and engaged,” Nancy says. “To me, it was a no-brainer to participate in a trial that could improve my care.” The sentinel node study led to a new standard for treating early-stage breast cancer.

Like many of the patients in the melanoma trial, Nancy had a complete response to the immunotherapy before her surgery. For that reason, plus the fact that she had some treatment side effects, Dr. Postow decided that Nancy didn’t need any further therapy after her surgery. Her scans show she is still cancer free.

Managing Melanoma Immunotherapy Side Effects

Because of the immunotherapy, Nancy’s adrenal glands were damaged. The adrenal glands regulate metabolism, the immune system, and other key functions in the body. To compensate, Nancy takes daily medication.

The immunotherapy also caused vitiligo, a condition in which the skin loses its pigment cells. “It might bother some people, but to me these things are minor, compared to your life,” Nancy says.

In general, the side effects experienced by patients in the trial were less severe than those seen with other immunotherapies. These side effects, when they do occur, result from the revved-up immune system damaging healthy tissues.

Another Melanoma MSK Patient Success Story

The side effects were relatively mild for another MSK patient in the trial — Jeffrey Kerman, a 77-year-old dentist from Long Island. He learned he had melanoma in 2019 after his wife noticed a dark spot on his chest. He immediately knew he wanted to be treated at MSK. “Everybody knows MSK is the best,” he says.

He saw melanoma surgeon Daniel Coit, who told him about the trial. Jeffrey was the first MSK patient to participate in the study.

Jeffrey Kerman

Thanks to a clinical trial at MSK, dentist Jeffrey Kerman is able to continue seeing patients.

He received his immunotherapy under the care of medical oncologist and melanoma expert Allison Betof Warner. He had two doses before his surgery and continued the treatment for a few months afterward. Jeffrey says his side effects were mostly muscle and joint pain, which felt similar to arthritis. The pain was treatable with small doses of steroids.

Almost three years after surgery, Jeffrey is no longer receiving any cancer treatment, and tests show no evidence of his cancer returning. He is able to have his follow-up blood work and scans at MSK Commack, which is much closer to his home.

Jeffrey’s father was also a dentist and worked until he was 81. “I’ve always said, ‘I’ve got to beat him and work even longer,’ ” Jeffrey says. “Thanks to MSK and this trial, I think I’ll be able to do that.”

“Because this drug combination is now FDA-approved for patients with advanced melanoma, we are able to offer it to many more people,” Dr. Postow says.

As for Nancy and Jeffrey, they feel fortunate to have been among the first to benefit from this new therapy, because they were patients at MSK.

This research was supported by the Melanoma Informatics, Tissue Resource, and Translational Pathology Core at the University of Texas MD Anderson Cancer Center and philanthropic contributions to the University of Texas MD Anderson Cancer Moon Shots Program. Dr. Postow is supported by a Cancer Center Support Grant (P30 CA08748) from the National Institutes of Health/National Cancer Institute. Dr. Ariyan is supported by a pilot grant from the Parker Institute for Cancer Immunotherapy at MSK. 

Dr. Postow has received consulting fees from Bristol Myers-Squibb, Merck, Array BioPharma, Novartis, Incyte, NewLink Genetics, Aduro, Eisai, and Pfizer and honoraria from Bristol Myers-Squibb and Merck. He also receives institutional support from RGenix, Infinity, Bristol Myers-Squibb, Merck, Array BioPharma, Novartis, and AstraZeneca. Dr. Ariyan has received a consulting fee from Iovance.