Tisagenlecleucel (Kymriah; Novartis Pharmaceuticals) is a CD19-directed 
genetically modified autologous T-cell immunotherapy. On August 30, 2017, the 
FDA approved tisagenlecleucel for treatment of patients up to 25 years of age 
with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory in 
second or later relapse. Approval was based on the complete remission (CR) rate, 
durability of CR, and minimal residual disease (MRD) <0.01% in a cohort of 63 
children and young adults with relapsed or refractory ALL treated on a 
single-arm trial (CCTL019B2202). Treatment consisted of fludarabine and 
cyclophosphamide followed 2 to 14 days later by a single dose of 
tisagenlecleucel. The CR rate was 63% (95% confidence interval, 50%-75%), and 
all CRs had MRD <0.01%. With a median follow-up of 4.8 months, the median 
duration of response was not reached. Cytokine release syndrome (79%) and 
neurologic events (65%) were serious toxicities reported in the trial. With 
implementation of a Risk Evaluation and Mitigation Strategy, the benefit-risk 
profile was considered acceptable for this patient population with such 
resistant ALL. A study of safety with 15 years of follow-up is required as a 
condition of the approval.See related commentary by Geyer, p. 1133.