CD-19 CAR-T cell therapy in adult B-cell ALL patients: A systematic review of clinical trials.

Abstract

e19012 Background: Chimeric antigen receptor T cell (CAR-T) therapy targeting CD19 has emerged as a transformative modality in treating B-cell malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), and inducing sustained responses. This review assesses the efficacy and safety of various CD-19 CAR-T cell therapies tested in adult relapsed/refractory B-cell ALL patients. Methods: A literature search was conducted on PubMed and Embase with keywords for “Acute lymphoblastic leukemia” and “CAR-T” from the inception of data till 1/1/2025. A total of 3,422 articles were identified. Two reviewers screened studies independently based on titles and abstracts, followed by a full-text review. Inclusion criteria were as follows: (1) prospective clinical trials involving adult patients (≥18 years) with B-ALL, (2) intervention with CD19-directed CAR-T cell therapy, and (3) reporting on clinical efficacy and safety outcomes. Exclusion criteria included case reports, case series, retrospective studies, preclinical research, and non-CD19 CAR-T studies. Results: Patients included in clinical trials were adults >18 years old, with relapsed/refractory (RR) ALL, ECOG performance status of less than 2. Complete remission (CR)/CR with incomplete hematological recovery(CRi) was achieved in 39/55 (71%) patients treated with KTE-X19, 113/147 (77%) with Obe-cel, 12/25 (48%) with UCART19, and 7/9 (77%) with GC007g. 1-year overall survival (OS) was 71% in patients treated with KTE-X19, 61% with Obe-cel, 56% with UCART19, and 85.7% with GC007g. Incidence of grade 3/4 cytokine release syndrome (CRS) was 13/55 (24%) with KTE-X19, 3/147 (2%) with Obe-cel, 6/25 (24%) with UCART19, and 1/9 (11%) with GC007g. Grade 3/4 immune effective cell associated neurotoxicity (ICANS) developed in 14/55 (25%) patients treated with KTE-X19, 12/147 (8%) with Obe-cel, 1/25 (4%) with UCART19, and 0/9 (0%) with GC007g. Conclusions: CD19 CAR-T cell therapies, including Obe-cel, KTE-X19, UCART19, and GC007g, have demonstrated efficacy and safety in the treatment of relapsed/refractory (RR) adult B-cell ALL patients. Among these, Obe-cel stands out with a lower incidence of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), making it a promising therapy for outpatient administration. However, large-scale, randomized, multi-center clinical trials are essential to validate these findings and further refine the role of CD19 CAR-T therapies in this high-risk population. Key characteristics and outcomes of clinical trials evaluating CD19 CAR-T cell therapy in adult B-ALL patients. Trial CAR-T N Median age Prior stem cell transplant CR/CRi 1-year OS CRS ICANS Shah et al. 2021 KTE-X19 55 40 23 39 39 13 14 Roddie et al. 2024 Obe-cel 127 37 56 99 77 3 9 Benjamin et al. 2022 UCART19 25 41 18 12 14 6 1 Roddie et al. 2021 Obe-cel 20 47 13 14 13 0 3 Luo et al. 2024 GC007g 9 41 9 7 8 1 0