As she hopped off the bleachers onto the grass after a graduation ceremony, Elizabeth Zarrella felt an unfamiliar pain in her back. A visit to the emergency room a week later revealed the source of the pain and the reason for its severity: her vertebrae were so brittle that two of them had been compressed by her modest jump.
It was a shock to one who, at age 45, had never before broken a bone, but, more ominously, was the first sign of a cancer that can require years of treatment. The cancer, multiple myeloma, also happens to be one whose treatment has been transformed by advances in immunotherapy. As a patient of Omar Nadeem, MD, Zarrella has been both a beneficiary of and participant in those advances, most recently as a recipient of two CAR T-cell therapies.
Following the discovery of her compressed vertebrae, Zarrella was admitted to the hospital, where doctors delivered a chilling — and, it turned out, incorrect — diagnosis. “They told me I had terminal ovarian cancer,” she relates.
That was quickly rectified when blood tests came back positive for multiple myeloma. “My doctors were amazed that my myeloma had reached the point at which it was diagnosed and I’d had no indication of it until those vertebrae were compressed,” says Zarrella, who lives with her husband in Easton. “The disease was so advanced, the doctors were afraid my kidneys were going to shut down.”
Zarrella underwent an autologous stem cell transplant in 2009 and transferred her care to Dana-Farber in 2011, first with Robert Schlossman, MD, then Nadeem. She was treated with a series of drug therapies to keep the disease under control. When it began to advance in 2021, Nadeem told her about a clinical trial of a new CAR T-cell therapy, an immunotherapy that uses genetically modified T cells to attack cancer.
“From the very beginning, Liz wanted to be proactive and contribute to the medical advances that have helped her fight this disease,” says Nadeem, clinical director of Dana-Farber’s Myeloma Immune Effector Cell Therapy Program. “She opted for the trial and was in one of the groups that received the lowest doses of the treatment. She did really well with it.”
Zarrella describes the process of making CAR T cells as “installing them with an intelligence that enables them to recognize cancer cells when they’re injected into the body.” In the therapy she received, that intelligence takes the form of a receptor that enables T cells to home in on tumor cells carrying the protein GPRC5D on their surface. The therapy grew out of work by Dana-Farber’s Eric Smith, MD, PhD, and his colleagues who, at Memorial Sloan Kettering Cancer Center, identified GPRC5D as a promising target and led the first trials of CAR T-cell therapies directed against it.
Zarrella was interested in the CAR T-cell therapy partly because it’s a one-and-done treatment: unlike the drug regimens she’d been on before, which required repeated visits to the hospital for treatment, CAR T involves a single infusion followed, hopefully, by an extended period of remission.
“As someone who was diagnosed at a young age and had been undergoing treatment for a decade, Liz had a perspective that led her to want to disconnect from the need to come in for therapy every week,” Nadeem remarks.
The treatment met those expectations. Within a week of being infused with the CAR T cells, “I felt so good, I could have gone back to work,” says Zarrella, an independent accountant in the construction industry.
When her cancer again began to progress early this year, she opted for the FDA-approved CAR T-cell therapy Carvykti, which targets the BCMA protein on myeloma cells. “It’s allowed me to get back to my life,” Zarrella relates. “I feel 100% healthy.” She’s working 30 hours a week and doing things she enjoys, like gardening, taking walks and bike rides, and reading.
“Liz is a caring, involved person,” Nadeem remarks. “She’s been really appreciative of the treatments that have been offered to her and very trusting of her medical team. We’ve all enjoyed working with her and getting to know her.”
About the Medical Reviewer
Dr. Nadeem completed his internal medicine residency training at Dartmouth-Hitchcock Medical Center and his hematology/oncology fellowship at the Warren Alpert Medical School of Brown University. He joined the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in 2018 where he is a Senior Physician and serves as the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and as the Clinical Director of the Center for Early Detection and Interception of Blood Cancers. He is an Assistant Professor of Medicine at Harvard Medical School and is board certified in internal medicine, hematology, and medical oncology. He is an Associate Director of the Myeloma Clinical Research Program and serves as a principal investigator on several clinical trials ranging from precursor plasma cell disorders to relapsed and refractory multiple myeloma. His research interests include MGUS and smoldering myeloma and immunotherapy in multiple myeloma, with particular focus on CAR T-cell therapy.