A second-generation CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy appeared to have clinical activity in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), according to the results of a phase 1 clinical trial recently published in Hematology Oncology.1
The trial (ClinicalTrials.gov Identifier: NCT02963038) included 10 pediatric patients with R/R B-ALL from the Hebei Second Provincial People Hospital in China. Fludarabine plus cyclophosphamide was the lymphodepleting regimen for all patients. Patients were infused with a second-generation CD19 CAR with a 4-1BB intracellular costimulatory domain at a median dose of 0.5 x 106 CAR-positive T cells per kg.
The study population had a median age of 6.5 years (range, 3-13 years) and received a median of 4 courses of chemotherapy (range, 3-10 courses). No patients previously received hematopoietic stem cell transplantation.
After the first month, 8 of the 10 patients (80%) achieved minimal residual disease negativity. Among the 8 patients, the median overall survival was 10.3 months and event-free survival was 4 months. However, 4 of the 8 patients relapsed within 3 to 4 months of CAR-T treatment.
As for toxicity, according to data in a table within the article, cytokine release syndrome occurred in all 10 patients, which included 1 grade 5 event and 3 grade 3 events. Neurotoxicity was seen in 6 patients, of which 2 were grade 3 and 1 was grade 4.
“To sum up, our study validates the safety and efficacy of CAR-T cell therapy targeting CD19 in ten pediatric patients, which encourage [sic] us to explore more patients with relapse/refractory B-ALL in the future,” the study authors wrote.
Ma F, Ho JY, Du H, et al. Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia [published online August 29, 2019]. Hematol Oncol. doi: 10.1002/hon.2672