Promise for ovarian cancer patients
Allegheny Health Network’s West Penn Hospital has an exercise room with a window overlooking the city. That’s where Lisa Zimmermann was often found, riding an exercise bike — during the two and a half weeks she spent at the hospital for an experimental treatmentfor ovarian cancer.
Zimmermann, 55, from Kansas City, Kan., is the second woman to enroll in the treatment, and the second to complete it. She entered the trial this spring with her abdomen riddled with tumors from stage 4 ovarian cancer, and is already showing promising results. In one area her doctors were targeting, the tumors are gone.
Ovarian cancer occurs when cells in the ovaries — usually epithelial cells — grow out of control. While ovarian cancer is not as common as other cancers like breast or skin cancer, it is the seventh most deadly, according to data from the Centers for Disease Control and Prevention, lung cancer being the deadliest. And it is the fifth deadliest among women.
From 2015 to 2019, around 11 per 100,000 Pennsylvanians died from ovarian cancer, which is more than many U.S. states. The American Cancer Society has estimated that in 2022, 19,880 new cases of ovarian cancer will be diagnosed in the United States and an estimated 12,810 women will die from the disease.
It’s likely that ovarian cancer is so deadlybecause by the time doctors catch it, the cancer has progressed into an advanced stage. All it takes to go from stage 2 to stage 3 cancer is one “little cell to float its way up,” said John Nakayama, a gynecological oncologist at Allegheny Health Network. With a gynecological cancer like uterine cancer, symptoms can include heavy bleeding, which might prompt a doctor visit, but ovarian cancer symptoms are often vague: bloating, nausea, constipation. And no approved screening methods for ovarian cancer exist. There are approved therapies to treat it, but surgery is risky if the cancer has drifted outside the ovaries, and doctors almost never use radiationfor ovarian cancer.
In the new trial at West Penn Hospital in Bloomfield, scientists are teaching patients’ own cells how to fight off ovarian cancer. The lead scientists supervising the trial are Nakayama and Yazan Samhouri, a hematologist at AHN’s Cancer Institute.
“Just like in your car, your cells have a brake and a gas,” Nakayama explained. “You can get cancer if you hold your foot down on the gas, or if your brake lines get cut.” Cancer cells dial down the immune system so the body can’t fight them off, he said.
For the new treatment, doctors remove T cells from tumors in a patient’s body and re-engineer them. T cells are one type of immune cell, produced in the bone marrow. They are involved in the body’s response to foreign substances, like cancer cells. Samhouri saidthat T cells are found inside tumors, as the T cells arrive to fight off the tumor but are disarmed by the intelligent cancer cells. The idea, he said, is to teach those T cells to avoid being suppressed and to outsmartthe tumor.
The first step of the treatment involves
“I think cancer is the best thing that’s ever happened to me. It opened my eyes to life and helped me to slow down. Everyone is in such a hurry.”
— Lisa Zimmermann
a screening to confirm a patient will be the right candidate. Once Zimmermann was approved, she underwent a surgery to remove the target tumor. Doctors shipped that tumor to a lab where they extracted the T cells and taught them to fight off cancer by stimulating them with DeTIL-0255, a drug-enhanced therapy made by the San Franciscobased company Nurix Therapeutics.
Zimmermann then received five days of chemotherapy to prepare her body for new cells coming. Doctors then injected the treated T cells back into her body in the form of an IV infusion.
She was then rushed to the intensive care unit (ICU) for a round of infusions of a protein called IL-2, which helps regulate and grow T cells in the body. Doctors monitored Zimmermann in the ICU because the IL-2 infusion can lower blood pressure. She stayed there for two and a half weeks and said her blood pressure fluctuated, bottoming out at times and making her feel terrible. Still, she wanted to get moving whenever she could, trying a combination of yoga, strength training and cardio — just a little each day.
The treatment takes about a month and a half, after which participants should receive follow-up scans to check the status of their cancer. And because this is a clinical trial, all medical expenses are paid. “This is such a great trial, I just wish more people knew
about it,” said Zimmermann.
As she is only the second woman in the U.S. to enroll in this clinical trial, the doctors want to recruit more patients. Patients are eligible if they have recurring ovarian cancer and have tried two prior lines of therapy. Patients must also have enough disease to biopsy. Researchers pick an “area to follow” in the body to see whether the treatment will reduce tumors in that area.
Zimmermann said her goal now is to get the word out to more women about the trial. “If you think something
is wrong, you should go get it checked,” she said. She barely had any symptoms: she was slightly bloated near her stomach and was spotting. Doctors told her she was probably going into menopause (she was 52 at the time), until a uterine biopsy came back as cancer, and a CT scan confirmed it. During surgery, doctors found that tumors proliferated throughout her entire abdomen. The surgeon removed two liters of fluid, stitched her back up, diagnosed stage IV cancer and told her the cancer was too widespread to operate. After
having exhausted five different lines of chemotherapy, she was excited to hear about the trial.
Zimmermann said the five consecutive days of chemo were the toughest part of the process. Usually, cancer patients sit for chemo for one or two days. Five
days of chemo depleted her immune system, said Zimmermann. The infusion of the T cells went great, though she said it “was like a production.” The T cells were inside just one IV bag, but 15 or so doctors milled about the room monitoring her condition.
Now almost five months later, her follow up scan results are in: there’s been a 47% reduction in her tumors, and doctors are hopeful the treatment will continue to work as time passes. She’ll have more blood work at West Penn in early November and will be back in three months for more CT scans. As for how she feels? Great. “Sometimes I forget I have cancer,” she said.
She had lived in Florida for 10 years and Pittsburgh for four, and she moved back to Pittsburgh on Oct. 25 after losing her new Florida apartment to flooding and mold from Hurricane Ian (she was hoping to return there for some post-chemo sunshine). She hasn’t seen many of her Pittsburgh friends yet, and said she was excited to surprise them with her new short, gray hair.
While Zimmermann’s results seem promising, Samhouri and Nakayama say it’s too early to determine how they feel about how the trial will progress with other patients. “We need to take our time,” Samhouri said. They’re hoping to recruit more patients for this trial and then move onto Phase II in the near future. Patients have been traveling from other states to be screened, and the trial is now recruiting patients in three other locations, including UPMC.
Nakayama said his field spent many years with no new approved treatments and added that this was an exciting time in oncology research. “It’s awesome that we’re putting women’s cancer front and center,” he said. “How many times does women’s cancer get to be first?”
“I think cancer is the best thing that’s ever happened to me,” Zimmermann said. “It opened my eyes to life and helped me to slow down. Everyone is in such a hurry.”
And because chemotherapy made her so nauseated, it forced her to get off electronics and be more present. “I probably wouldn’t have made it if I had a negative outlook,” she said. “I’m 55 years old, and I feel like I’m starting a new life.”