A CD7-targeted chimeric antigen receptor (CAR) T-cell therapy was “safe and highly effective” in heavily pretreated T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma (LBL), according to a recent clinical trial.
Xian Zhang, MD, of the Beijing Lu Daopei Institute of Hematology and the Hebei Yanda Lu Daopei Hospital in China and colleagues conducted the research.
They developed a “novel fratricide-resistant approach to derive naturally selected 7CAR-T cells (NS7CAR) from bulk T-cells without additional genetic manipulations” and tested it in phase I/II clinical trials.
They screened 57 patients with relapsed or refractory T-cell ALL or T-cell LBL for the study between December 2020 and May 2022. Of those 57 patients, four did not receive NS7CAR due to rapid disease progression (n=1), production failure (n=1), or personal reasons (n=2). Those four patients were not included in the analysis.
Dr. Zhang and colleagues collected peripheral blood mononuclear cells from patients (n=51) or a transplant donor (n=2) by leukapheresis and purified T cells with magnetic beads. All patients received intravenous fludarabine 30 mg/m2 daily and cyclophosphamide 300 mg/m2 daily for three days before the NS7CAR infusion.
A total of 53 patients, including 34 with T-cell ALL and 18 with T-cell LBL, received an NS7CAR T-cell infusion. Most patients (90.5%) received bridging chemotherapy to “control rapid disease progression,” the study’s authors wrote.
The median patient age was 22 years old. Of the 53 patients, nearly half (47.1%) had high-risk phenotypes and genotypes, while 45.2% had extramedullary disease. The patients received a median of five prior lines of therapy.
The transfection efficiency was 90% (range, 40.7%-100%). Most patients received a dose of 5 × 105 cells/kg (n=24) or 1.5 × 106 cells/kg (n=28), while one patient received a dose of 2 × 106 cells/kg.
The median follow-up time was 206 days. Nearly all (95.8%) of patients achieved minimal residual disease (MRD)-negative complete remission (CR) in bone marrow/peripheral blood by day 28. Of the 24 patients who had extramedullary disease, 20 responded, including 13 who had a CR and seven who had a partial response (PR) at a median of 33 days postinfusion.
The 18-month overall survival (OS) rate was 75%, while the event-free survival (EFS) rate was 53.1%. After infusion, 32 patients (60.3%) bridged to receive consolidation allogeneic hematopoietic stem-cell transplantation (HSCT) within three months. Those patients had an 18-month OS rate of 75.8%, while the EFS was 71.5%.
Among the 21 patients who did not undergo consolidation allogeneic HSCT, seven patients remained in CR for a median of 88 days, while 11 patients who had less than a CR received salvage transplantation. Of the remaining three patients, two died within five months and one patient was “lost to follow-up” after six months, according to the researchers.
A total of eight patients relapsed, five of whom lost CD7 expression. Of the six patients with SCL-interrupting locus (STIL)-T-cell acute leukemia (TAL1) fusion genes, four relapsed within one to three months, and three of those four patients lost CD7 expression.
Most patients (88.7%) had mild cytokine release syndrome (CRS), while five patients had grade 3 CRS and one had grade 4 CRS.
“Our phase I/II study shows that NS7CAR therapy is safe and highly effective in patients with heavily pretreated [relapsed or refractory T-cell] ALL/LBL, including those with extramedullary involvements and a history of prior [allogeneic] HSCT,” the study’s authors concluded. “Patients with STIL–TAL1 tend to have a poorer response and early relapse. When relapse occurs, loss of CD7 expression was observed.”
Zhang X, Yang J, Li J, Qiu L, Li J, Lu P. Analysis of 53 patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) treated with CD7-targeted CAR-T cell therapy. Blood. 2022;140(Supplement 1):2369-2370. doi:10.1182/blood-2022-158878