Margaret is energetic and engaging. At 92-years-old, she is mentally sharp and physically active. She is an avid reader, walks for 45 minutes each day, takes strength training and balance classes and volunteers in her community.
In 2016, a bump on the back of her neck threatened to change all of that. What Margaret and her doctor thought was a simple cyst turned out to be a rare and aggressive form of skin cancer called Merkel cell carcinoma. Her surgeon recognized the seriousness of the diagnosis and advised her to get to Johns Hopkins right away.
Johns Hopkins head and neck cancer surgeon Dr. Wayne Koch confirmed the diagnosis. “My son asked him, ‘If it was your mother, who would you tell her to see,” and he answered, ‘Bill Sharfman. He’s the best,’” says Margaret.
Dr. Sharfman, the Mary Jo Rogers Professor in Cancer Immunology and Melanoma Research and the Director of Cutaneous Oncology (cancers related to or affecting the skin) at the Johns Hopkins Kimmel Cancer Center, is an international leader in the treatment of the most difficult types of skin cancers, including melanoma, advanced basal cell cancers and Margaret’s cancer, Merkel cell cancer.
Merkel cell cancer is classified as an orphan disease because it is diagnosed in fewer than 2,000 people a year in the U.S. and, until recently, had no treatments with long-term benefit. “It tends to occur in older people and those who have suppressed immune systems, says Dr. Sharfman. “Most Merkel cell cancers are caused by a virus called Merkel cell polyomavirus, and the rest are caused by sun exposure and other unknown factors.”
Standard chemotherapy works in about half of Merkel cell patients, but responses are often short-lived, with cancers recurring after just a few months. Side effects from chemotherapy are common and difficult for many patients and can be even more troublesome for older patients. This was a major concern for Margaret. “At my age I had no interest in going through chemotherapy,” she says.
Dr. Sharfman explained to her that if she did nothing the cancer would likely take her life in six months or less. “That got my attention,” Margaret says.
Fortunately, Dr. Sharfman had another plan in mind. A relatively new and much better tolerated type of cancer treatment called immunotherapy was demonstrating promising results in patients with Merkel cell carcinoma. A new clinical trial was studying an immunotherapy drug called pembrolizumab in Merkel cell cancers to see if it worked better than standard chemotherapy. Dr. Sharfman recommended Margaret for the trial.
“This is the type of therapy you can offer to a 91-year-old patient because I knew it was well tolerated. The chances of a major side effect were low, and there was a very good chance that it would help her in a meaningful way. There was no reason not to try it,” says Dr. Sharfman.
The mother of four talked it over with her children, and they all agreed it was the right approach. Margaret, who got the last slot available for the clinical trial was also the oldest patient in the study.
Two of Margaret’s grandchildren were graduating college, and she had plans to attend. Not even cancer was going to stop this devoted grandmother from these events, but once the graduations were over, Margaret began immunotherapy, receiving 30-minute infusions of the drug every three weeks in the outpatient clinic.
Immunotherapy is different than traditional cancer treatments. Rather than killing dividing cells—both cancer cells and healthy cells—immunotherapy targets immune cells, helping the immune system recognize and go after cancer cells.
Much of the key science is unfolding in the Kimmel Cancer Center’s Bloomberg~Kimmel Institute for Cancer Immunotherapy, where experts Suzanne Topalian, Evan Lipson, Janis Taube and others are studying an immune system brake called PD-1 and drugs that release that brake in Merkel cell and other cancers. PD-1 is known as an immune checkpoint that dampens the immune process and prevents autoimmune disease, but it also interferes with the immune response to cancer. Drugs like pembrolizumab block PD-1, unleashing an immune attack against cancer cells.
These drugs are new, and there is still much research left to do. To that end, Margaret and other patients on the study volunteer to provide blood and tumor samples that further the understanding of how these drugs work, which may help researchers devise ways to make them work even better and in more patients. Margaret says she likes the idea that what the doctors and researchers learn from this clinical trial may also help others diagnosed with Merkel cell cancer.
One year into treatment, Margaret’s cancer isn’t completely gone, but immunotherapy knocked it back and has held it in check, keeping it from spreading. The clinical trial calls for her to receive infusions of the drug for another year.
“The beauty of immunotherapy is that it keeps working even after treatment is stopped,” says Dr. Sharfman. He hopes Margaret’s awakened immune system will continue to patrol for Merkel cell cancer cells indefinitely and to keep her cancer in check.
Although immunotherapy does not work for every patient, in those who respond, it often provides long-lasting control of the cancer with fewer side effects than chemotherapy, particularly the quality-of-life altering ones that have framed cancer treatment for decades.
Still, Dr. Sharfman cautions that side effects can occur, when the heightened immune activity may cause inflammation or other irritations to normal tissue and organs. Most common side effects are minor and easily managed, he says. Kimmel Cancer Center experts are trained to pick up on them early and work with the many experts throughout Johns Hopkins to manage them. Even severe cases are manageable with expert attention. “It’s one of the advantages of being in a place like Johns Hopkins. There is great collaboration among all medical specialties, and this has been particularly helpful when managing immunotherapy side effects,” says Dr. Sharfman.
In fact, Margaret experienced a side effect a few months into her treatment. She was panicked when her vision became impaired, fearing she would lose her sight. “It was like looking through a fog,” Margaret explains. Dr. Sharfman immediately referred her to a Johns Hopkins Wilmer Eye Institute expert who was able to correct the problem quickly with prednisone eye drops and over-the-counter moisture drops.
Other than regular trips to the Kimmel Cancer Center, Margaret says, “I’ve gone on with my life exactly the way that it was before I was diagnosed with cancer.”
The grandmother of eight and great grandmother of four has another college graduation next year and a law school graduation in three years. “I told Dr. Sharfman he has to keep around for that,” Margaret quips.
As Margaret jokes, her children cannot help but reflect on what could have been if immunotherapy wasn’t an option. “We feel blessed,” says Margaret’s son. “Dr. Sharfman gave us our mother back.”
“My children and I cannot say enough good things about Dr. Sharfman, my nurse Trish Brothers, and really all of the people at the Kimmel Cancer Center. We have been so impressed. My son has worked with many hospitals and he says he has never seen such a wonderful culture,” says Margaret. “There are no words to express how grateful we are.”
For Dr. Sharfman, immunotherapy has provided the opportunity to help so many more patients. “This is the most exciting thing,” he says. “In these aggressive skin cancers, we have gone from helping about five percent of patients with chemotherapy to 50 percent of patients, and that’s all because of immunotherapy.”