Studies show that individuals diagnosed with ulcerative colitis have approximately a twofold increased risk of developing colorectal cancer compared with the general population. A study investigating treatment with autologous chimeric antigen receptor (CAR) T cells targeting the CD19 antigen in a single patient found that the treatment appears to have induced rapid drug-free remission in refractory ulcerative colitis. The findings will need to be confirmed in a larger study to evaluate the safety and efficacy of this therapy, and whether certain subgroups of patients are particularly prone to treatment response. The study by Müller et al was published in The New England Journal of Medicine.
Study Methodology
The researchers investigated CAR T-cell therapy targeting the CD19 antigen in a 21-year-old woman with severe multidrug-resistant ulcerative colitis who had declined a colectomy. Her previous treatments included prednisolone, mesalamine, infliximab, ustekinumab, ozanimod, filgotinib, vedolizumab, upadacitinib, and cyclosporine combined with mirikizumab, which had not induced a clinical remission.
Because previous studies had shown dysregulated mucosal B-cell responses in ulcerative colitis, the researchers decided to treat the patient with the CD19-directed T-cell engager blinatumomab, which resulted in only a transient amelioration of disease activity. To enhance the depth of B-cell depletion, the researchers proceeded with an infusion of autologous CD19 CAR T cells, which resulted in peripheral and mucosal B-cell depletion.
Results
Following the CAR T-cell therapy, the patient experienced clinical and biochemical remission, which were both maintained over the 14-week follow-up period without the use of concomitant therapy. Endoscopic, histologic, and ultrasonographic assessments showed signs of mucosal healing over time. The patient gained nearly 20 pounds in body weight and was able to resume her professional activities.
Except for a grade 1 event of cytokine-release syndrome on day 3 of her treatment, which resolved spontaneously, the patient did not experience acute toxic events that were deemed related to the CAR T-cell therapy.
“These data suggest the possibility that CD19 CAR T-cell therapy can induce rapid drug-free remission in refractory ulcerative colitis, a disease that was previously thought to be largely B-cell–independent, given that rituximab treatment showed no efficacy. Because these findings are based on a single case, more patients with ulcerative colitis will need to be treated with CD19 CAR T cells to interpret the safety and efficacy of this treatment, and to evaluate whether certain subgroups of patients are particularly prone to treatment response,” concluded the study authors.
Markus F. Neurath, MD, of the Friedrich-Alexander University Erlangen–Nuremberg, in Erlangen, Germany, is the corresponding author of this study.
Disclosure: The study authors’ conflict of interest disclosures may be found at NEJM.org.
