Donor-derived, CD7-directed, chimeric antigen receptor (CAR) T-cell therapy had “encouraging activity” but led to reversible, low-grade graft-versus-host disease (GVHD) in 40% of patients with relapsed/refractory acute lymphoblastic leukemia/lymphoma, according to results of a phase II trial.
Yue Tan, of the Institute of Hematology and Blood Diseases Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues conducted the research and presented their findings at the 64th American Society of Hematology Annual Meeting and Exposition.
The researchers enrolled 20 patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. Patients who previously underwent hematopoietic stem cell transplantation (HSCT) received CAR T-cells from their prior HSCT donor, whereas those who had not undergone HSCT received CAR T-cells from new donors who also provided stem cells for transplantation after CAR-T therapy.
The researchers evaluated the efficacy and safety of the target dose, which was 1×106, plus or minus 20%, CD7 CAR T-cells per kg of body weight. The study’s primary end point was efficacy, and the secondary end point was safety.
Grade I-II GVHD, which was considered a short-term adverse event, occurred in 40% of patients but was reversible in all cases.
With a median follow-up of 11 months, 90% of patients responded. The best overall response rate was 90% at 3 months. The objective response rate was 90% at 1 month and 3 months after infusion.
Of the patients who responded, 67% received no further therapy, 16.6% remained in remission, 38.9% had a relapse, and 11.1% died of infection. All patients had “continuously detectable CAR T-cells until the last visit,” according to the study’s authors.
Nearly half (44%) of patients proceeded to HSCT, and no CAR T-cells were detectable after HSCT. Of the patients who received HSCT, 62.5% remained in remission, 25% relapsed, and 12.5% died of an infection.
The 1-year progression-free survival rate was 62.3%, and the 1-year overall survival (OS) rate was 60%. The median time to relapse was 4 months. Patients without mediastinal mass had significantly longer OS than patients with mediastinal mass.
Grade III or higher cytokine release syndrome occurred in 10% of patients. Severe adverse events occurred in 16.6% of patients who responded to the treatment.
“Interim results from a phase II trial of donor-derived CD7 CAR T-cell therapy showed similar encouraging activity in treating [relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma] with [the] phase I trial,” the study’s authors concluded. “Relapse emerges as [a] major issue impeding long-term outcomes. CD7-negative relapse was commonly observed under CAR T-cell surveillance. Late-onset GVHD and infections may occur and should be carefully managed. Patients with mediastinal mass had poor overall survival and [need to be] further investigated.”
Tan Y, Pan J, Deng B, et al. Efficacy and safety of donor-derived CD7 CAR T cells for r/r T-cell acute lymphoblastic leukemia/lymphoma: interim analysis from a phase 2 trial. Abstract #2011. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.