Mark, Stage 4 Melanoma, & a Personalized Vaccine Clinical Trial

“Bad news, it’s in your lungs.”

It was Mark Lashway’s oncologist circling back around with news from his most recent scan. He remembers this moment clearly; his melanoma was back and it was worse than ever.

The news came as a shock. He had a serious brush with melanoma a few years earlier, and was vigilant about keeping up with his checkups. He felt fine, but the other shoe had dropped.

Now, with tumors invading his left lung, he had advanced to Stage 4 melanoma.

“I’d been warned the first time around that once [melanoma] got to your lungs, brain, or bones that was usually it,” remembers Mark. “That’s all that kept going through my head.”

Mark’s journey with melanoma began three years earlier, when he noticed a pimple on his chest. When he finally got it checked out by a dermatologist he was shocked to hear that it was cancerous. 

“I had no idea what melanoma was or how serious it could be,” says Mark. “I just thought it was skin cancer and could be easily cut out and I’d be done with it.” 

After having the melanoma surgically removed and Sentinel Lymph Node Biopsy to determine if it had spread to nearby lymph nodes, his doctors concluded that it was Stage 2B. They encouraged him to undergo a year of interferon, or adjuvant therapy, as a follow-up to reduce the risk of melanoma returning.

Interferon was the first FDA-approved adjuvant therapy for melanoma and is an early immunotherapy. Using a genetically engineered human protein, it stimulates the immune system to detect and attack melanoma with the goal of stopping, or delaying, its return. Interferon isn’t used widely today due to its severe side effects and grueling dosing schedule that requires patients to get an infusion five-days a week for the first month and three-days a week for the following 11.

For Mark, interferon was unbearable. Sixteen infusions into his first month, he landed in the Emergency Department with severe bleeding. After five days in the hospital recuperating, he and his doctor agreed that interferon wasn’t for him. They decided to monitor the situation carefully – a strategy called, “watch and wait.” 

Prior to the FDA approval of modern melanoma treatments in 2011, ‘watch and wait’ was a commonly used strategy for melanoma. We just didn’t have tolerable treatments that were proven to be effective for most people. Mark was monitored carefully for three years, and then the day he was dreading had finally come: his scans detected his melanoma had metastasized to his left lung.

Now, with Stage 4 melanoma, Mark was fully aware of what he faced, Mark decided to take no chances. Instead of being treated at a local hospital, he – and his wife Mary Ann – made the trek to Dana-Farber Cancer Institute four hours away at his brother Ross’ urging. At Dana-Farber, Mark met with and was treated by doctors who had extensive experience treating melanoma and were aware of and actively participating in ongoing research to find new, better treatments.

First, Dr. Daniel Weiner, a surgical oncologist, removed the left upper lobe of his lung that had been invaded by melanoma; taking approximately 20% of his lung function. Then, Mark met with Dr. Patrick Ott, Clinical Director of the Melanoma Center at Dana-Farber and lead researcher on the BJ’s Wholesale Club-MRA Team Science Award.

The melanoma treatment landscape had dramatically changed in the three years since Mark was first diagnosed. New options such as checkpoint immunotherapies and molecularly targeted therapies had earned FDA approval and many other approaches were actively being tested in clinical trials.

One such treatment, in a phase 1 clinical trial, was a new type of personalized vaccine that researchers hoped would train the immune system to better find and attack melanoma. The vaccine, coined NeoVax, was made specifically for each patient over a twelve-week period.

Understandably, Mark was very concerned about side effects of any potential treatment. “I just couldn’t go through what I had with interferon again,” says Mark. 

Dr. Ott explained that because the vaccine is custom made for each patient, the immune response it elicits is directed only against the tumor and not healthy tissues. 

“I wasn’t keen about this being a phase 1 trial,” says Mark. “But when I was told that I was a good candidate, I jumped on the opportunity because Dr. Ott was objective, clear, and I trusted him.” 

To develop these personalized vaccines, Ott and his team first sequence the genome of each patient’s melanoma tumor. Then, they identify the mutated genes in that patient’s tumor and select from them the targets most likely to elicit a strong immune response. The selected targets represent the pool of so-called neo-antigens that the NeoVax is aimed at. Because the mutations are only present in the patient’s tumor, the immune response is directed only against the tumor and not other, healthy tissues. “The technology needed to do this in time for patients, just didn’t exist ten years ago,” said Ott. “This is the ultimate form of personalized medicine.”

Over the course of six months, Mark and five other patients each received 5 priming and 2 booster vaccinations with their own, personalized vaccine. They also would get four injections weekly during this period. At Mark’s last injection, he also received a full body scan. Unfortunately, the scans showed that three new tumors had formed just outside his left lung.

Dr. Ott stressed cautious optimism and explained that despite the new growths, the vaccine may still prove successful at priming Mark’s immune system for checkpoint immunotherapy.

Three months later, after monthly infusions with pembrolizumab (Keytruda®) that were intended to work synergistically with the vaccine, Mark was back in the exam room waiting for Dr. Ott and his scan results. 

He remembers Dr. Ott saying: “I have the best news a doctor can give you about melanoma, you responded 100% to the therapies.”  

Mark continued receiving monthly pembrolizumab infusions for the next three years. Scan after scan continued to show No Evidence of Disease (NED). Today, four years later, he’s still melanoma free. 

“I’ve always had a good attitude and thought I’d get through this,” says Mark. “But when this all happened – I have to be honest – it really tested me,” says Mark. 

“But now, at the end of this, I can say that melanoma brought an awful lot of good into my life. In some ways, maybe it was a gift.”