The Immunotherapy Revolution

ADVANCES IN IMMUNOLOGY HAVE MADE IT POSSIBLE TO CURE DEADLY MELANOMA SKIN CANCER.

BY NANCY BRANDS WARD / PHOTOGRAPHED BY SHANE O’DONNELL

Tracy Stoll has lived her life with one overriding fear: melanoma. While Southern Californians pay close attention to protecting their skin from sun damage, not everyone lives in constant fear of a dangerous skin cancer that is expected to kill more than 7,000 Americans in 2021. Because Stoll has many freckles and moles, she has been scrutinizing her skin and visiting a dermatologist every six months since age 5.

“I was 8 when I had the first mole removed on my foot,” says the 45-year-old Montecito mother of two sons and one daughter. “I’ve had basal cell cancers removed from my hand and hairline. I always thought melanoma was one of those things I could control if I just stayed on top of it.” In 2015, however, she received the diagnosis she’d dreaded. What she didn’t know then was that recent advances in a type of cancer treatment called immunotherapy would save her life.

The Saint John’s Cancer Institute has a long history of pioneering work on cancer immunotherapies, beginning decades ago when the organization was founded as the John Wayne Cancer Institute. Throughout the years, dedicated philanthropic support helped researchers push the envelope with leading-edge experiments, and Saint John’s was proud to count itself as immunotherapy pioneers as breakthrough drugs finally emerged in recent years.

IT STARTED WITH A SKIN-COLORED BUMP

Stoll was fortunate in a sense because melanoma was one of the first areas to benefit from progress in cancer immunotherapy. A little over five years ago Stoll noticed a skin-colored bump on her shin. She thought it looked a lot more like a wart than skin cancer, so she was careful not to scratch it or shave over it. Six months later while on a trip to Hawaii, Stoll noticed another wart-like bump beside the first one. It started bleeding the next day. “I knew I hadn’t bumped it,” she says. “I know that warts don’t just spontaneously bleed.”

She immediately saw her dermatologist upon return from Hawaii, who was inclined to freeze it off because it looked like a wart, but Stoll insisted she take a sample. During the visit she also biopsied something on Stoll’s back. Five days later she learned the bump on her shin was melanoma. However, the cancer was designated as stage 1B—an early stage in which most patients don’t experience a recurrence after treatment.

She met with specialists at Saint John’s Cancer Institute at Providence Saint John’s Health Center, including Leland Foshag, MD, a professor of surgery and director of the Complex General Surgical Oncology Fellowship program at the institute. A surgical oncologist with expertise in melanoma, sarcoma and other cancers, Dr. Foshag made a four-inch incision in Stoll’s shin to excise cancerous cells and removed one of the lymph nodes in her groin. There was no sign of cancer in her lymph nodes.

However, about a year later a few tiny bumps on the shin sent her back to Dr. Foshag. The bumps didn’t look like melanoma, but the surgery revealed melanoma tumors. A third surgery removed more cancer from the shin. This time when they examined the lymph nodes in Stoll’s groin, they found traces of melanoma in one. The cancer had spread. Dr. Foshag removed four lymph nodes. “Now we were at a complicated point in deciding what to do,” Stoll says, who handles the business aspects of the upscale Irene Neuwirth jewelry company. “They’d removed all the cancer, but it was obvious that there were still cancer cells in my body.”

Since early in this ordeal, Stoll relied on her husband, Robert, to guide her decisions about treatment. A lawyer with decades of experience reading medical records, he also has the savvy to understand articles in medical journals. They sought second opinions from the other top melanoma specialists in Los Angeles. But she found their approaches cold and frightening. “They said because the cancer was in my lymph node, the chances that one cell was left behind is extremely high and that the cancer will spread to my brain and to my liver if I did nothing,” she says. “I’ve never been so scared in my life. It was like a self-fulfilling prophecy—melanoma is something I’ve feared all my life. I felt totally hopeless. That made me recognize that the team I had at Saint John’s was the team I needed to take me through this journey. We told the Saint John’s team we wanted to start aggressive treatment.”

DRUG COMBINATION UNLEASHES IMMUNE RESPONSE

Three months after her second and third surgeries in January 2017, Stoll began immunotherapy treatment at Saint John’s under the care of former institute director Steven O’Day, MD. Dr. O’Day is a highly regarded melanoma specialist with experience in both immunotherapy research and treatment. He prescribed a two-drug combination of ipilimumab and nivolumab, which has been used over the past five years to successfully treat melanoma. The immune system doesn’t recognize cancerous cells as foreign, so it doesn’t attack them, says Kim Margolin, MD, medical director of the melanoma program at Saint John’s Cancer Institute at Providence Saint John’s Health Center. And even if it does recognize them, it shuts off the immune response.

These two drugs exploit that process by allowing the body to recognize cancerous cells and spurring the immune system into action, Dr. Margolin says. Pioneering basic research on cancer immunotherapies began more than 25 years ago at Saint John’s, under the leadership of the late Donald L. Morton, MD, the institute’s cofounder. The institute was one of the few medical centers in the country pursuing the complexity of cancer immunotherapy research. “These drugs completely revolutionized treatment of melanoma,” explains Przemyslaw W. Twardowski, MD, professor of medical oncology and urologic oncology and director of clinical research, urology and urologic oncology at Saint John’s Cancer Institute. “Before immunotherapy, the prognosis was dismal in the vast majority of melanoma patients when the cancer had spread—with survival less than a year. Now we are curing more than half of melanomas that have invaded various organs. She was lucky she got it when she did.”

Sometimes these powerful drugs kick the immunesystem into such high gear that it overreacts and attacks other organs. This happened to Stoll; her skin and pituitary gland came under attack, and she had to stop treatment after just two of the four scheduled sessions and take a heavy dose of steroids for two months. Nevertheless, it was enough. “What is interesting about this particular regimen is that sometimes even one or two doses can have a profound, very durable effect on the cancer,” Dr. Twardowski says. It did for Stoll. A few weeks after her second immunotherapy treatment, she watched over two weeks as her tumor tripled in size, became red hot and sensitive to the touch, then dissolved. “That’s the immune system performing its function,” says Dr. Twardowski.

“These drugs completely revolutionized treatment of melanoma. Before immunotherapy, the prognosis was dismal … now we are curing more than half of melanomas that have invaded various organs.”

A CARE TEAM LIKE FAMILY

The Saint John’s health care providers and staff made her feel supported and secure throughout her cancer journey, recovery and survivorship, Stoll says, adding that Dr. O’Day and Dr. Foshag gave her hope and encouragement.

“They’re like family. They were both very supportive of all the things I did—the hot yoga, meditation, vegetarian diets and acupuncture twice a week. Dr. O’Day would ask, ‘Don’t you want to rest?’ And I’d reply, ‘I’m in fight mode, and when I’m at war, I’m at war!’” Every day now, Stoll wakes up grateful for the treatment she received from the multidisciplinary team at Saint John’s. “I’ve developed an incredible appreciation for my body and the strength it had to kill my cancer,” she says. “I tell my body how grateful I am and that I will never take it for granted.” A heightened connection with her body is one thing that has resulted from Stoll’s cancer experience. She meditates and listens to what her body is telling her, whether it’s to slow down, get more sleep or ask a doctor to check out any pain she experiences.“People who have survived cancer learn a powerful lesson about how they’re living life and what changes they need to make to survive,” Stoll says, “And if you don’t take the opportunity to look at it, it would be a great misfortune.” She’s now focused on doing all the things she loves outside of work—traveling, cooking, yoga, hiking, skiing, boating—and most of all creating memories for her children.

She isn’t completely free of fear: “I always have that fear in the back of my mind.” But she remains cancer-free and now simply returns for scans every two years. Stoll and her husband continue to support the work at the Saint John’s Cancer Institute through financial donations. “I’m a huge fan of Saint John’s and their doctors,” Stoll says. “Everyone was so kind and genuinely interested in me and my husband and what we were going through and most importantly, I trusted them with my life.”

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