Matthew Frank, MD, PhD, discusses the rationale for investigating CD22-directed CAR-T cell therapy in adult patients with large B-cell lymphoma who relapsed after or were refractory to CD19-directed CAR T-cell therapy.
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.