Chimeric Antigen Receptor T Cell Therapy in Patients with Multiply Relapsed or Refractory Extramedullary Leukemia.

Autologous CD19-directed chimeric antigen receptor T lymphocyte (CAR-T) therapy is an approved and effective treatment for the management of patients with refractory and multiply relapsed B cell precursor acute lymphoblastic leukemia (B-ALL). Experience using this therapy in pediatric patients with extramedullary (EM) disease is limited, in part because these patients have frequently been excluded from clinical trials owing to concerns for an increased risk of immune effector cell-associated neurotoxicity syndrome (ICANS). We infused 7 patients with refractory or multiply relapsed B-ALL who presented with isolated EM relapse with tisagenlecleucel. Six patients had isolated central nervous system (CNS) leukemia, and 1 patient had an isolated testicular relapse. An initial complete response was seen in all patients, with 5 patients remaining in CAR-T-induced remission at a median of 18 months from first infusion. Reversible ICANS was seen in 1 patient with CNS leukemia. Durable B cell aplasia occurred in 3 patients, with a median time to B cell recovery of 6.5 months in the other patients. These data suggest that CAR-T therapy has promising safety and efficacy in treating EM leukemia, although definitive conclusions are limited by the small size of the cohort and limited follow-up period.