Results of <scp>ARI</scp>‐0001 <scp>CART19</scp> cell therapy in patients with relapsed/refractory <scp>CD19</scp>‐positive acute lymphoblastic leukemia with isolated extramedullary disease
Valentín Ortiz‐Maldonado, Anna Alonso‐Saladrigues, Marta Español‐Rego, Nuria Martínez‐Cibrián, Anna Faura, Laura Magnano, Albert Català, Daniel Benítez‐Ribas, Eva Giné, Marina Díaz‐Beyá, Juan Gonzalo Correa, Montserrat Rovira, Mercedes Montoro‐Lorite, Alexandra Martínez‐Roca, Luis Gerardo Rodríguez‐Lobato, Raquel Cabezón, Joan Cid, Miquel Lozano, Enric García‐Rey, Núria Conde, Georgina Pedrals, Marı́a Rozman, Montserrat Torrebadell, Xavier Setoaín, Sónia Rodríguez, Jordi Esteve, Mariona Pascal, Álvaro Urbano-Ispizúa, Manel Juan, Julio Delgado, Susana Rives
Abstract
Abstract We evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B‐cell acute lymphoblastic leukemia (B‐ALL) treated with the CD19‐directed CAR T cells ARI‐0001 in two centers (adult and pediatric), including patients treated in the CART19‐BE‐01 trial and the consecutive compassionate use program. iEMD was detected by PET‐CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 10 6 ARI‐0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure‐related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%–99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%–94%) of them. Progression‐free and overall survival were 49% (95% CI: 30%–79%) and 61% (95% CI: 40%–92%) at 2 years. In conclusion, the use of ARI‐0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products.