Dual Targeting CD19/CD22 CAR T-Cell Therapy Is Effective for ALL

A study presented at the 2020 ASH Annual Meeting assessed the safety of a dual-targeted CD19/CD22 chimeric antigen receptor (CAR) T-cell therapy and found that it was safe and effective for patients with relapsed/refractory acute lymphocytic leukemia (ALL). 

Researchers conducted a retrospective, case-controlled analysis at the First Hospital of Soochow University. From Oct. 2017 to July 2020, 36 patients were enrolled in the single center, open-label, phase I/II study. More than half of the cohort (58.3%) received more than four prior therapies, and eight patients underwent hematopoietic cell transplantation (HCT). All patients received fludarabine, 30 mg/m2 and cyclophosphamide 300 mg/m2 on days one through three pre-infusion. 

Patients then received a novel tandem CD19/CD22 CAR-T construct with CD28 and OX40 co-stimulatory domains, with a median infusion dose of 1×107cells/kg (range, 0.5-2.5×107cells/kg). Each patient with an active disease who was treated with CD19/CD22 CAR T-cell therapy was matched with a control who received CD19 CAR T-cells from Jan. 2017 to Sept. 2019. All patients underwent bone marrow examination 28 days post-infusion. 

After tandem CD19/CD22 CAR-T infusion, all patients achieved complete remission (CR); the minimal residual disease (MRD)-negative CR rate was 77.8%. Six- and 12-month overall survival (OS) rates were 88.36% and 70.6%, respectively, and six- and 12-month leukemia-free survival (LFS) rates were 88.072% and 69.216%, respectively.

Patients who underwent HCT after CAR T-cell therapy (n=25; 82.309%) improved one-year LFS rates compared with those who did not subsequently undergo transplant (n=11; 31.169%; P=0.0135).

Adverse events were mild and were relieved with supportive treatments, according to the authors. Eight patients developed grade 3/4 cytokine release syndrome, and two patients had hemophagocytic lymphohistiocytosis, but these resolved with low-dose steroids.

The CR rate was higher in CD19/CD22 CAR T-cell group than in CD19 CAR T-cell group (100% vs. 53.57%; P=0.000), as was the MRD-CR rate (71.43% vs. 42.86%; P=0.000). The six-month OS rate was 69.276% in the CD19/CD22 CAR T-cell group versus 53.571% in CD19 CAR T-cell group. Seven and four patients relapsed, respectively.

“It is possible that multitargeted CAR T-cell therapy may overcome this resistance mechanism and improve clinical outcomes,” the researchers concluded.

Reference

Cui W, Zhang X, Dai H, et al. Tandem CD19/CD22 Dual Targets CAR-T Cells Therapy Acquires Superior CR Rate Than CD19 CAR-T Cells: A Case Controlled Study. Abstract 1937. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, Dec. 2-11, 2020.