Dr Frank on the Background of Investigating CAR22 Therapy in Relapsed/Refractory LBCL

Matthew Frank, MD, PhD, assistant professor, medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, discusses findings from prior research investigating a CD22-directed CAR T-cell therapy (CAR22) that informed the rationale for launching a phase 1 trial (NCT04088890) with this agent in patients with relapsed/refractory large B-cell lymphoma (LBCL).

At the 2023 EHA Congress, investigators shared results from a single-institution trial evaluating the use of CAR22 in patients with relapsed/refractory LBCL who have progressed on a prior CD19-directed CAR T-cell therapy. Notably, 41 patients were enrolled in the trial, and 1 patient withdrew from the study, leaving 40 evaluable patients. Of these patients, 38 had successful CAR22 manufacturing. Moreover, the investigators reported that CAR22 elicited an overall response rate of 68% at a median follow-up of 22.8 months, and 53% of patients achieved a complete response.

Although CD19 is an attractive target for CAR T-cell therapy, it can become downregulated, and its expression can be lost, Frank begins. Therefore, seeking alternative antigens is important, as there are many patients who would benefit from enrolling in clinical trials investigating therapies with other targets, Frank explains. Potential targets include CD22, CD20, CD79a, and CD79b, making for a lot of options for investigators to consider when designing future trials, he adds.

CD22 is highly and uniformly expressed in most B-cell malignancies, including lymphoma, Frank expands. Investigators launched this phase 1 trial based on this previous knowledge, as well as previous impressive results derived from the National Cancer Institute, which evaluated the same CD22-directed CAR T-cell therapy in children with leukemia, he emphasizes. Notably, this previous research revealed high response rates with CAR22, Frank says. Therefore, the phase 1 trial investigators were interested in evaluating the efficacy of this agent in adult patients with leukemia and lymphoma, Frank concludes.