Tisagenlecleucel: The First CAR on the Highway to Remission for Acute Lymphoblastic Leukemia

Tisagenlecleucel is a first-in-class chimeric antigen receptor (CAR) T-cell therapy approved by the US Food and Drug Administration in 2017 for relapsed/refractory (RR) acute lymphoblastic leukemia (ALL) in patients up to 25 years of age. Tisagenlecleucel is an autologous T-cell therapy that is genetically engineered with a lentiviral vector to seek and eliminate CD19-expressing B cells throughout the patient’s body and retain antitumor immune surveillance following remission. This groundbreaking cellular therapy brings unprecedented single-agent efficacy to patients with RR ALL, citing complete response rates of greater than 80% and 6-month relapse-free survivals exceeding 60% in a patient population with poor prognosis and few treatment options. Patients receiving CAR T-cell therapy are at risk for cytokine release syndrome (CRS), neurotoxicity, and infections, along with other toxicities that may be severe or life-threatening. The cornerstone of the management of moderate to severe CRS is treatment with the interleukin-6 antagonist tocilizumab, with dramatic responses often occurring within 24 hours. The optimal management of neurotoxicity following tisagenlecleucel remains undefined. It is critical that providers caring for patients receiving tisagenlecleucel understand the multistep process to prepare a patient for therapy, how to closely monitor patients for toxicity, and how to manage emergent adverse events following cell infusion.