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The University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC) has a long and distinguished history of advancing the field of cancer care. Among the center's recent advances are pioneering work into aromatase inhibitors and the development of GammaPod radiation therapy for breast cancer.

UMGCCC and clinicians from the University of Maryland School of Medicine (UMSOM) are now turning their attention to the next frontier of cancer treatment: chimeric antigen receptor T cell therapy, also known as CAR-T therapy. The approach, which collects a patient's own T cells and genetically engineers them to destroy cancer cells, has the potential to revolutionize current therapeutic modalities for blood cancers and, eventually, for other cancer types as well.

"UMGCCC has dozens of clinical trials underway using cellular immunotherapy for all blood cancers and some solid tumors, and we are developing at least three types of 'next-generation' CAR-T products," said Aaron Rapoport, MD, the Gary Jobson Professor in Medical Oncology at UMSOM and Transplant and Cell Therapy Director at UMGCCC.

Researchers from UMGCCC recently co-authored a study entitled "Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma," published in The New England Journal of Medicine. The study investigated the effectiveness of CAR-T therapy as a second-line treatment for people with refractory or early relapsing large B-cell lymphoma.

Patients with large B-cell lymphoma that does not respond to chemotherapy, or who relapse less than a year after chemotherapy, have a historically poor survival rate. The study randomly assigned patients to receive standard second-line therapy or CAR-T therapy. The groups were evenly split, with 179 patients receiving standard care and 180 patients receiving CAR-T. The study tracked event-free survival, overall survival, response, and safety.

The CAR-T patients benefited from increased survival rates and higher response to treatment. More patients responded to the CAR-T therapy (83 percent) than the standard therapy (50 percent). A 24-month follow-up analysis revealed that the patients who received CAR-T had an event-free survival rate that was more than four times as long as the patients who got standard care (8.3 months and 2.0 months, respectively). Two years after treatment, the CAR-T patients' event-free survival rate was 41 percent, compared to 16 percent with standard treatment.

"About 50 percent of patients with otherwise untreatable, aggressive lymphoma, leukemia and myeloma experience long remissions after CAR-T therapy, and many of these patients are likely to be cured," Dr. Rapoport said.

UMGCCC is a national leader in CAR-T therapy. As of 2021, the center has treated more than 250 cancer patients with engineered CAR-T and other T cells. Many of these patients had relapsed and had refractory forms of blood cancers, leaving them with no other viable treatment options. Some of these patients have survived for almost five years – and counting – after the conclusion of treatment.

Upon FDA approval, UMGCCC was also the first in the U.S. to treat a patient with 2nd line axicel/axicabtagene based on the study.

"We were the first cancer center in the Maryland-Delaware-Virginia tri-state area and the 20th in the nation to be qualified to offer CAR-T therapy to patients with aggressive lymphoma," Dr. Rapoport said. "CAR-T therapy is a remarkable advance for patients with relapsed and advanced blood cancers, but there is much more work to do. Hopefully in the future, CAR-T also will be an option for patients with other forms of cancer."

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