Jan 8, 2016
01:24 PMHealth & Science
A Connecticut Woman’s Tragedy Inspires Breakthroughs in Immunotherapy Cancer Treatment at Yale
Melissa Marottoli, above, was diagnosed with stage four lung cancer at 26, but didn't let that stop her from living her life. She got married and helped inspire cutting-edge cancer research.
It was the type of news no patient wants to hear: Tests showed that Melissa Marottoli, a 26-year-old Guilford native, had stage four lung cancer, an incurable condition expected to end her life within a year.
Dr. Scott N. Gettinger, an oncologist at Yale-New Haven, was tasked with sharing the awful news with Melissa and her family in 2007. Known as “Mel” to her friends and family, Melissa was a vivacious and an outwardly healthy nonsmoker. At that time she was the youngest patient to whom Gettinger had ever given such a dire diagnosis.
“You see this wonderful young woman who has her whole future in front of her and she’s given this diagnosis of metastatic [cancer that has spread] lung cancer, which is just unthinkable,” Gettinger recalls. “To tell a young person that their prognosis is limited is a hard thing to really swallow.”
Melissa has a large immediate family and close extended family. The day Gettinger delivered the news there were so many family members present there was not room for them all in his office.
“We were shocked and we were really confused,” recalls Andrea Viscuso, Melissa’s cousin.
But amidst that devastating sense of shock, something else welled up within Melissa and her family—determination.
(Above: Melissa, right, kisses her twin sister Lindsay on the cheek in this childhood picture.)
The American Lung Association estimates that 158,040 Americans died of lung cancer in 2015. It’s a type of cancer that accounts for about 27 percent of all cancer deaths—more than colorectal, breast and prostate cancers combined. It is also the second leading cause of death in the U.S. behind heart disease. Though often misconstrued as a smoker’s disease, 20 percent of women and 10 percent of men who are diagnosed with it are, like Melissa, nonsmokers.
Like many cancers, the origins of lung cancer can be mysterious. Doctors do not know what contributed to Melissa’s cancer or why she got the disease when her identical twin sister, Lindsay Marottoli Greenberg, did not.
Gettinger is a member of the thoracic oncology program at the Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. In addition to seeing patients, he researches new cancer treatments and works with pharmaceutical companies to conduct trial studies. He is part of a multidisciplinary team that received an $11 million research grant from the National Cancer Institute for research into immunotherapy treatments for lung cancer, a type of treatment designed to boost the body’s natural defense system and harness it to fight cancer.
“For the immune system to mount an attack on a cancer, it has to recognize the tumor. Once it recognizes the tumor, it mobilizes its immune cells, the soldiers of the immune system. Then those immune cells find where the infection or the cancer is, and they attack it,” Gettinger says. “But along this circuit are these so-called immune checkpoints that serve to dampen the immune response to either infection or cancer. [Under normal circumstances] this serves to protect us. For example, if you have an infection, you eradicate the offending organism but then you have to pull back the immune system because if you don’t you’re going to have excessive inflammation, and you could also develop autoimmunity where the immune system is going to attack itself. In cancers, these immune checkpoints can, in a sense, be hijacked and cancers can use these checkpoints to protect themselves from the immune system.”
The goal of immunotherapy treatments, explains Gettinger, is to block these checkpoints so the immune system can do its job. “It is in a sense unleashing the immune system so it can attack cancer,” Gettinger says.
Last fall, two drugs that Gettinger researched during clinical trials at Yale were approved by the Federal Drug Administration for certain forms of lung cancer treatment. One is Nivolumab and is being manufactured by Bristol-Myers Squibb under the trade name Opdivo, while the other is Pembrolizumab and is manufactured by Merck under the trade name Keytruda.
Unlike chemotherapy, the drugs showed limited side effects during trials, and for some patients, there were near miraculous results. In one trial of patients with advanced lung cancer and life expectancies of only 3 to 6 months, 18 percent of those who took Nivolumab were alive after three years. In another trial, the median duration of response was 17 months, with some responses ongoing beyond five years. In December, former President Jimmy Carter credited Keytruda with shrinking his brain tumors completely.
“If they work, they can work in some patients for years,” Gettinger says. “We started doing these trials five or six years ago and we still have patients from the first trial that do not have any evidence of a disease. So the potential of these therapies is enormous.”
In 2007, these treatments were not available for Melissa, but with the support of her family she was determined not to succumb to the disease. They asked doctors not to share her prognosis, as they didn’t want the negative news impacting their outlook.
“For us, with Melissa getting diagnosed so young, we really felt like if we could keep her alive long enough science would catch up. That was our mantra,” says Kristen Marottoli Peck, Melissa’s older sister. They began to look anywhere and everywhere for a treatment that might help. The family was also approached by a variety of organizations offering potential cures, but sometimes their motives were suspect. “Some people were well-intentioned; other people were trying to make some money off of us,” Kristen says.
Melissa and her family decided to pursue as many nonharmful treatments as possible. She followed juicing and vitamin regimes and received conventional treatments. Along with her twin Lindsay, Melissa traveled to the Institute for Tumor therapy in Duderstadt, Germany, and The Institute of Hyperthermia and Immunotherapy in Vienna. She received an experimental twin-based treatment that attempted to use Lindsay’s white blood cells to boost Melissa’s response to the cancer.
Melissa had the Italian words fede, speranza, vita and amore (Italian for faith, hope, life and love) tattooed on her arm, which became her mottos, and her faith and compassion became an inspiration to her family.
While waiting for treatments she would spend time comforting and praying with other patients. “One time she sat next to a woman who didn’t speak any English and she just stayed with her,” Kristen says.
No one’s sure which treatment stuck, or exactly what helped, but Melissa began beating the odds. She lived one year, then two, then three, then four, then five years. She stayed connected with old friends from high school and college and continued to make new ones everywhere she went. “She had a heart that was one of the biggest hearts that I’ve ever seen, she wanted everyone to be healthy and live a long life,” Lindsay says. “When she would come to the hospital, the doctors and nurses would be excited to see her.”
After being diagnosed, Melissa reconnected with Matthew Hogan, whom she had dated in college, and they began to date again. They were married in August 2012. But Melissa’s cancer had continued to spread. By the time of her wedding, her lungs were so overridden with cancer that doctors were surprised she was able to walk. She died on Dec. 9, 2012.
Soon afterward, her family formed the nonprofit Melissa Marottoli Hogan Foundation. “My way of still fighting for her was to start this foundation,” Lindsay says, adding that she still has trouble talking about her twin in the past tense. “I know that Mel really wanted awareness. Lung cancer has really become more common in young women and she wanted to make sure no one else suffered what she went through.”
The organization, which will hold its annual gala on March 5 at Woodwinds in Branford, has donated more than $100,000 to Gettinger’s research at Yale. The goal is to donate an additional $50,000 over the next year.
Gettinger says, thanks in part to that funding, the immunotherapy drugs now available are already changing treatments. “There’s a major, major change in the way in which we’re approaching all cancers. I think we will see over the next 10 and 20 years significant strides in what we can do for cancer. One goal of cancer care is can you turn cancer into a chronic condition? Or even can we cure metastatic cancer? Although we’re not there yet we’re certainly making strides.”
If that happens it would be the ultimate legacy for Melissa’s spirit.
“Living without her is still pretty difficult,” Lindsay says. “Here’s someone who was given such terrible circumstances and she tried to make the most of every single day. She had an amazing spirit and all she wanted to do was help others.”