Video

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

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.

Related Videos
Yair Lotan, MD, UT Southwestern Medical Center
Alan Tan, MD, Vanderbilt-Ingram Cancer Center
Alex Herrera, MD
Roy S. Herbst, MD, PhD
Sheldon M. Feldman, MD
Laura J. Chambers, DO
Thomas Westbrook, MD
Massimo Cristofanilli, MD, attending physician, NewYork-Presbyterian Hospital; professor, medicine, Weill Cornell Medical College, Cornell University
Fred Saad, CQ, MD, FRCS, FCAHS, director, Prostate Cancer Research, Montreal Cancer Institute, Centre Hospitalier de l’Université de Montréal; full professor, Department of Surgery, Université de Montréal; uro-oncologist, Urology Department, University of Montreal Health Center
Ajay K. Nooka, MD, MPH, FACP