Dr. Frank on the Rationale for CD22-Targeted CAR T-cell Therapy After CD19 Relapse in LBCL

Matthew Frank, MD, PhD, assistant professor, medicine, the Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, discusses the rationale for investigating CD22-directed CAR-T cell therapy (CAR 22) in adult patients with large B-cell lymphoma (LBCL) who relapsed after or were refractory to CD19-directed CAR T-cell therapy.

A phase 1 trial (NCT04088890) investigated autologous CAR 22 in evaluable patients, including those who relapsed after or are refractory to CD19-directed CAR T-cell therapy. Findings presented at the 2023 Transplantation and Cellular Therapy Meetings showed that CAR 22 elicited an overall response rate (ORR) of 68%, including ORRs of 66% at dose level 1 of 1 x 106 CAR+ cells/kg and 78% at dose level 2 of 3 x 106 CAR+ cells/kg. The complete response rate was 53% in all patients, 52% at dose level 1, and 56% at dose level 2.

Although 3 CD19-directed CAR T-cell therapies have been approved by the FDA for patients with LBCL, including tisagenlecleucel (Kymriah), lisocabtagene maraleucel (liso-cel; Breyanzi), and axicabtagene ciloleucel (axi-cel; Yescarta), relapsed following those treatments remains an issue for patients, Frank adds.

A major reason for relapse is down regulation or loss of the target, CD19. Therefore, investigators pursued treatment for patients who have relapsed by targeting a different antigen on their tumor, Frank notes. CD22 is expressed in the majority of LBCLs and other malignancies, Frank says.

CD22-directed CAR T-cell therapy had previously displayed efficacy in pediatric patients with leukemia, Frank says, adding that these children were predominantly treated with allogeneic stem cell transplant or CD19-directed CAR T-cell therapy, but had relapsed. This led investigators to design a clinical trial for adult patients with LBCL who predominately relapsed after CD19 CAR T-cell therapy, Frank concluded.

Editor's Note: Dr Frank reports participation on scientific advisory boards for Adaptive Biotechnologies, Kite-Gilead, and Cargo; and industry-contracted research for Allogene Therapeutics, Adaptive Biotechnologies, and Kite-Gilead.