How CAR T-Cell Therapy Gave Cherie Rineker Her Life Back
In 2012, when her life seemed at its best, it was suddenly devastated by a diagnosis of an incurable blood cancer, multiple myeloma, Cherie Rineker, of Lake Jackson, Texas, told CONQUER: the patient voice, in an interview.
When she was first diagnosed, Cherie said, her oncologist told her that some patients with multiple myeloma can reach remission (meaning the cancer stops progressing) after a few months of treatment. But after 5 years and more than 12 types of chemotherapy, she realized that she wasn’t one of those lucky patients.
After receiving a total of 13 different types of chemotherapies and different combinations of chemotherapy regimens, her body was slowly declining. “Although the different treatments had kept me alive for 5 years, I realized that the cancer and the treatments were slowly killing me,” Cherie said.
Despite incredible progress in treatments, chemotherapy still attacks our body cells indiscriminately, destroying healthy cells in addition to the cancer cells. So, in December 2017 she decided she didn’t want any more chemotherapy, Cherie says, but she wasn’t ready to give up on life, either.
She recalled a news program she had watched about a patient with multiple myeloma who was treated with a new type of therapy, using the measles virus. She was intrigued by that unusual treatment, which introduced her to the concept of CAR T-cell therapy, a new type of immunotherapy in which the patient’s own blood cells are taken to a lab to be re-engineered, and then infused back into the patient’s bloodstream to fight the cancer cells.
T-cells are a type of lymphocytes (or white blood cells) that are part of the immune system and can identify invading foreign bodies, like infection or cancer cells. CAR T-cells are designed to recognize markers (or biomarkers) on the surfaces of infectious or malignant cells and attack these cells. One such marker in multiple myeloma is called B-cell maturation antigen, or BCMA.
“This led me to the idea of finding and enrolling in a clinical trial with a CAR T-cell therapy, which gave me new hope,” Cherie said.
A Race Against Time
The process of joining a clinical trial felt daunting, Cherie says. In addition to the very specific requirements, most hospitals had long waiting lists and required travel to the hospital site just to see if she even qualified. A good friend put Cherie in touch with Brian McMahon, founder of SparkCures, an organization that helps patients with multiple myeloma find clinical trials. This led her to Sarah Cannon Cancer Center in Nashville, Tennessee, where oncologist Jesus Berdeja, MD, was doing a phase 2 clinical trial with CAR T-cell therapy for people with multiple myeloma.
Finding a trial ended up being the easy part; getting accepted to the trial was the hard part. So Cherie wrote an e-mail to Dr. Berdeja to explain why she wanted to be in his trial. She thought that it was important that he knew her not only as a patient and her lab reports, body scans, and an extensive history of previous treatments, but also as a wife, a mother, and a unique person whose life mattered to her children, husband, friends, and loved ones.
She also attached an article she wrote, “Dying to Get into a Trial,” describing the challenges of getting into a CAR T-cell clinical trial. In addition, “My dear friend did die while waiting to get into a CAR T-cell trial. That loss devastated me, and I didn’t want the same thing to happen to my family,” Cherie said.
The next day she received a personal message from Dr. Berdeja. He thanked her for her letter, and a couple of days later she had an appointment at his office. After the appointment, the research nurse told her that more than 30 patients were on the list ahead of her, waiting to get into the trial. She knew she didn’t have that kind of time.
It was a long shot, but a few days later Cherie got a call telling her she could be the next candidate to join the trial. She didn’t know what happened to the other 30 patients. She knew one, her friend, who had passed away. Others might not have passed the rigorous qualifications. Some might have gone back to chemo. Dr. Berdeja and Cherie use her story as an example to show that no matter how long your shot is at getting into a clinical trial, you should not get discouraged, but keep trying.
Qualifying for the CAR T-Cells Process
To qualify for the CAR T-cells trial, Cherie’s myeloma biomarker count had to be at a certain number; her immune system had to be strong enough; and her lungs, heart, and kidneys had to be healthy enough to handle the fight that would surely happen once her re-programmed and re-engineered T-cells were infused back into her body.
In addition, because her absolute neutrophil count, or ANC, was low, she had to show she could climb stairs to qualify. Exercise, such as climbing stairs, helps to activate the neutrophils (the type of white blood cells that protect against infection) in the bloodstream. Cherie’s neutrophils had to be high enough to show that her immune system would be able to get through the re-programming of her T-cells. She had to climb stairs on 3 different occasions to qualify, and she did.
Cherie’s T-cells were harvested in early February 2018, which was done through a process called leukapheresis that spins off white blood cells and returns the rest of the blood back to the patient. The procedure required that she had a catheter put in her neck the day before. The harvesting of her T-cells took about 4 hours. Except for some serious tingling in her hands, feet, and mouth because of an electrolyte imbalance, which was alleviated by a calcium infusion, and because her blood was being circulated through a machine outside the warmth of her body, and then returned at a lower temperature requiring many blankets to stop her teeth from chattering, all went well.
When her T-cells were collected and taken to the lab, a new genetic coding was inserted into the T-cells, which turned her T-cells into a mixture of her own genetic code and the new code inserted into the T-cells. These new CAR T-cells were programmed to identify and kill the myeloma cells in Cherie’s blood, by targeting the BCMA expressed on the cancerous cells.
Once her T-cells were transfected (the process of introducing nucleic acids into the T-cell), they were cultured (pumped up) and expanded in a lab for 4 weeks, where they turned into hundreds of millions of new T-cells.
As her CAR T-cells were multiplying in a Petri dish, she was given a temporary (bridge) chemotherapy, because her myeloma cells were multiplying out of control. However, the chemotherapy did not work, which was a very scary time. The stress, the pain, the opioids (given for pain), the uncertainty, the fear—this was all too much. She had so much faith in this clinical trial, but she had so much faith in all the treatments she had previously received, and none worked for long.
“As I waited,” Cherie said, “my health deteriorated fast. I was not sure if I would ever see my daughter again.” Cancer is horrible at any time; having young children during cancer makes it even more challenging, she said.
Cancer Free, at Last
Finally, on March 7, 2018, Cherie started the 3 days of a lymphodepleting chemotherapy regimen, which was needed to eradicate the old leftover T-cells in her blood, so they could make way for the new CAR T-cells; she was given back her genetically modified T-cells.
A week later, the fog lifted, and she felt great, she says. The numbers that tracked her cancer had made a sharp dive and were now below normal. “This showed what I was already feeling—for the first time since my diagnosis, I was cancer free, which was then confirmed by my next bone marrow biopsy and PET scan,” Cherie said.
CAR T-cell therapy taught Cherie’s immune system to fight multiple myeloma within weeks. “What 2 stem-cell transplants and 13 other treatments had not been able to do in more than 65 months, CAR T-cell therapy did in less than 1 month,” she said.
Cherie says she doesn’t like to call herself a patient with cancer or a survivor anymore. “I don’t say I am in remission. Instead, I say I am cancer free,” she said. She hopes that her genetically modified T-cells will continue to fight any potential relapses, to provide her long-term protection from cancer.