The cell therapy brexucabtagene autoleucel is the third CAR T-cell therapy to be approved by the FDA; UCLA Health is one of the few institutions in the U.S. to provide all three therapies. The other therapies are tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia and axicabtagene ciloleucel for the treatment of certain types of non- Hodgkin’s lymphoma.
CAR T-cell therapy works by training a person’s own immune system to fight cancer cells by genetically modifying the T-cells to recognize and attack the cancer. It’s a “living therapy” that stays inside the body to keep killing tumor cells long after the cells are infused in the body. “CAR T-cell therapy is a gamechanger for mantle cell lymphoma since just a single treatment yields an excellent response rate,” says oncologist John Timmerman, MD, a member of UCLA’s Jonsson Comprehensive Cancer Center. “While it is too early to know if some of these patients have been cured, it is likely that the combination of CAR T cells with other treatments will lead to even better results, with even more durable remissions.”
Mantle cell lymphoma represents about 6 percent of all non-Hodgkin’s lymphomas. While most cases are viewed as incurable, treatment is aimed at obtaining long remissions with each line of available therapy. Most treatments require many months of therapy to achieve tumor shrinkage, but with just one infusion of brexucabtagene autoleucel CAR T cells, “patients go into remission and stay in remission longer when compared to the clinical trials of the other available treatments,” says Sarah M. Larson, UCLA oncologist and a Jonsson Center member.
Like most cancer treatments, the therapy is not without potential side effects, including fever, chills, malaise and potentially low blood pressure and organ toxicity, as well as neurotoxicity, which includes such symptoms as confusion, drowsiness and speech difficulties, with severe cases leading to seizures and coma. Dr. Timmerman says that UCLA has designed a unique therapy trial to mitigate neurotoxicity. “Overall, side effects of CAR T-cell therapies are manageable, and ongoing research is teaching us how to make this novel treatment easier to tolerate,” he says.
Since UCLA first started treating patients with CAR T cells in 2016, the field has progressed rapidly. Dr. Larson notes that UCLA has been at the forefront of progress in the field. “In addition to industry-sponsored trials and commercially available products, we also design, develop and manufacture our own CAR T cells to improve patient outcomes,” she says.
“Patients who have run out of other treatment options are often put into remission with CAR T-cell therapy,” Dr. Timmerman adds. “Unfortunately, most still eventually relapse, so there is still much work to be done.”
New strategies being explored at UCLA offer promise for even more potent therapies to benefit more patients. “Our multipronged efforts at UCLA to improve both the efficacy and safety of CAR T-cell therapy are aimed at making a continued impact on this fast-evolving field,” Dr. Timmerman says.