Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
Level 4 - case-series / case-control
Single-arm, uncontrolled multicenter phase 2 trial
PubMed 29385370 · doi:10.1056/NEJMoa1709866
What was done
In an open-label, single-cohort, phase 2 trial across 25 global centers, 75 pediatric and young adult patients with CD19+ relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) received an infusion of tisagenlecleucel and were evaluated for efficacy. The primary endpoint was the overall remission rate (complete remission or complete remission with incomplete hematologic recovery) within 3 months.
What was found
The overall remission rate within 3 months was 81%, with all responding patients achieving minimal residual disease negativity on flow cytometry. Event-free survival was 73% (95% CI, 60 to 82) at 6 months and 50% (95% CI, 35 to 64) at 12 months. Overall survival was 90% (95% CI, 81 to 95) at 6 months and 76% (95% CI, 63 to 86) at 12 months. Median duration of remission was not reached, and tisagenlecleucel persisted in blood for up to 20 months. Suspected treatment-related grade 3 or 4 adverse events occurred in 73% of patients. Cytokine release syndrome occurred in 77% (48% received tocilizumab), and neurologic events occurred in 40% (no cerebral edema reported).
Why it matters
This study establishes that tisagenlecleucel produces high, minimal residual disease-negative remission rates with durable persistence in young patients with relapsed or refractory B-cell ALL who have few therapeutic alternatives.
Limits
The study is an uncontrolled, single-arm trial without a direct comparator group. The evaluated cohort was limited to 75 infused patients, and high-grade toxicities were frequent, requiring intensive management.