A single infusion of the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced durable remissions in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic lymphoma (ALL), according to the results of a phase II study published in the New England Journal of Medicine.
Within 3 months of CAR T-cell infusion, 81% of patients were in remission and all of these patients were negative for minimal residual disease.
“The treatment of patients who have relapsed or refractory B-cell ALL after failure of two regimens is challenging,” wrote researcher Shannon L. Maude, MD, PhD, of the department of pediatrics at Perelman School of Medicine at the University of Pennsylvania, and colleagues. “The rate of minimal residual disease–negative overall remission of 81% and the 6-month overall survival rate of 90% found in this study of tisagenlecleucel compare favorably with the rates achieved with Food and Drug Administration–approved agents for relapsed B-cell ALL.”
A phase I/IIa study of tisagenlecleucel showed that patients with relapsed or refractory B-cell ALL had high rates of complete remission. However, the treatment was associated with serious toxic effects. The phase II study was a 25-center, global study in 75 pediatric and young adult patients who received an infusion of tisagenlecleucel. The median age of patients was 11.
The median duration of follow-up for patients was 13.1 months. Among those patients with at least 3 months follow-up, the overall remission rate was 81%. Sixty percent of patients achieved complete remission and 21% had complete remission with incomplete hematologic recovery. In addition, all patients who had a best overall response of complete remission were negative for minimal residual disease.
At 6 months, event-free survival was 73% and overall survival was 90%; at 12 months, these rates were 50% and 76%.
The majority of patients (73%) experienced grade 3/4 adverse events suspected to be related to tisagenlecleucel infusion. These events included cytokine release syndrome, which occurred in 77% of patients; 48% of these patients received tocilizumab. The median time from onset of cytokine release syndrome to grade 3/4 level was 3 days.
“Although nearly half the patients received care in an ICU, the criteria for admission to the ICU varied widely across institutions,” the researchers wrote. “A total of 25% of patients were treated with high-dose vasopressors, a treatment commonly administered in intensive care settings.”
In addition, 40% of patients experienced neurologic events and were managed with supportive care. The researchers noted that “most neurologic adverse events were transient, did not include cerebral edema, and appeared to be more frequent in patients with higher-grade cytokine release syndrome.”