CAR T Cell Therapy as a Definitive Consolidation for Older Adults with B-ALL in First Complete Remission

We report a phase 1 study assessing safety and efficacy of CD19 chimeric antigen receptor (CAR) T cells as definitive consolidation in older adults (≥55 years) with B-cell acute lymphoblastic leukemia (B-ALL) in first complete remission (CR1) (ClinicalTrials.gov identifier: NCT05707273). Eighteen patients received lymphodepletion followed by infusion of memory-enriched CD19 CAR T cells. The median age was 64 years, and all patients were measurable residual disease (MRD)-negative pre-lymphodepletion. There were no dose limiting toxicities, grade ≥2 cytokine release syndrome or any grade immune effector cell-associated neurotoxicity syndrome. Estimated 18-month event-free and overall survival were 84% and 100%, respectively. CAR T cells expanded in blood and cerebrospinal fluid despite patients' MRD-negative status. Comparing clinical samples from patients with relapsed/refractory (R/R) B-ALL from our historical trial (NCT02146924) and patients in CR1, we found that the blood and CAR T cell products from R/R patients were hyper-inflammatory and hyper-immunometabolic, respectively. First line CAR T cell therapy was safe, well-tolerated, and potentially extended remission in patients in MRD-negative CR1. These findings support further investigation of early use of CAR T cell therapy for B-ALL.