Patient Dies After Developing Resistance to CAR T-Cell Therapy

A young patient with B-cell acute lymphocytic leukemia who received chimeric antigen receptor (CAR) T-cell therapy developed a resistance to his treatment, according to a report published in Nature Medicine. The patient ultimately died of complications from his disease.

When successful, the revolutionary CAR T-cell therapy allows physicians to remove a patient’s T cells, genetically alter the cells, and reintroduce them into the patient’s body. In the reported case, a leukemic B cell was extracted and modified along with the T cells. While the T cells attacked the patient’s leukemia as intended, the reintroduced B cell was resistant to the CAR T-cell treatment and slowly proliferated, eventually leading to the patient’s death.

Jos Melenhorst, PhD, an immunology expert at the University of Pennsylvania and a co-author of the report, emphasized that the case occurred during the early days of clinical CAR T-cell therapy use, and that improvements in technology allow manufacturers to more effectively exclude B cells. The version of the treatment that ultimately received regulatory approval uses an updated manufacturing process designed to ensure that only T cells are modified and reintroduced.

In a statement to STAT News, Jason Westin, MD, of the MD Anderson Cancer Center, expressed optimism that the incident would not slow the development of CAR T-cell therapies. “[CAR T-cell therapy] data [are] one of the most exciting things we’ve seen in cancer in forever,” said Dr. Westin, who was not involved in the report. “Having rare theoretical things that actually happen is concerning, but it should in no way temper the potential for the future of CAR T cells.”

Sources: STAT News, October 1, 2018; Ruella M, Xu J, Barrett DM, et al. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med. 2018;24:1499-1503.