A global study showed durable remission with long-term persistence in pediatric and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) after a single infusion of a chimeric antigen receptor (CAR) T-cell therapy.
A previous phase I-IIa study demonstrated high rates of complete remission and an association of serious but reversible adverse events in children and young adults with relapsed or refractory B-cell ALL after infusion with the anti-CD19 CAR-T therapy tisagenlecleucel. Further analysis is needed to validate these findings.
Shannon L Maude, MD, PhD, Children’s Hospital of Philadelphia, and colleagues conducted a phase II, single-cohort, 25-center, global study examining the effects of tisagenlecleucel in pediatric and young adult patients with CD19-positive relapsed or refractory B-cell ALL. A total of 75 patients received a single infusion of tisagenlecleucel and were evaluated for overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months.
The study was published in The New England Journal of Medicine (online February 1, 2018; doi:10.1056/NEJMoa1709866).
Results of the study showed an overall remission rate within 3 months of 81%, with all patients who had a response to CAR-T therapy found to be negative for minimal residual disease assessed by flow cytometry.
Event-free survival and overall survival at 6 months were 73% (95% CI, 60-82) and 90% (95% CI, 81-95), respectively. At 12 months, those rates decreased to 50% (95% CI, 35-64) and 76% (95% CI, 62-86). Median duration of remission was not reached.
Dr Maude and colleagues also noted that persistence of tisagenlecleucel in the blood was observed for up to 20 months.
Grade 3/4 adverse events associated with tisagenlecleucel occurred in 73% of patients. Among the notable toxicities were cytokine release syndrome (77%) treated with tocilizumab in 48% of patients and neurologic events (40%) managed with supportive care. No cerebral edema was reported.
“In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects,” authors of the study concluded.—Zachary Bessette