Chimeric antigen receptor (CAR) T-cells targeting CD19 have shown impressive outcomes in refractory/relapsed B-cell acute lymphoblastic leukaemia (r/r B-ALL) ; however, frequent relapse demands multi-targeted approaches. We report Spanish clinical data on the safety and efficacy of tandem anti-CD19/CD22 CAR T-cells administered on a compassionate use basis in a cohort of 10 heavily pretreated paediatric, adolescent, and young adult (AYA) patients with r/r B-ALL. Most (9/10) of the patients had relapsed B-ALL, 7 having received previous anti-CD19 CAR T-cell therapy and 6 haematopoietic stem cell transplantation (HSCT). Two patients had Down syndrome. Increased high-grade CRS/ICANS and proinflammatory markers (IL-6, LDH and ferritin) correlated with patients with a high tumour burden (TB) before lymphodepletion. Complete remission on day +28 post-infusion was achieved in 8/10 patients (7 with MRD-), and 5/7 patients received HSCT as consolidative therapy within three months post-infusion. Two patients with early relapse after tandem anti-CD19/CD22 CAR received rescue therapy and HSCT. At the 18-month follow up, overall survival (OS) was 70% (95% CI, 47%-100%). Tandem anti-CD19/CD22 CAR T-cell administration combined with consolidative HSCT is a promising therapeutic approach, though managing bridging therapy and reducing the TB prior to infusion remain key challenges (REALLCART trial, NCT06709469, EudraCT 2023-509723-41-01). This work was supported by a grant from the Instituto de Salud Carlos III to APM PI22/01226, two grants from CRIS Cancer Foundation to Beat Cancer as part of the projects "Advanced Cell Therapy Unit Hospital Universitario La Paz" and JM "Proyecto Mateo: CAR T-cell therapy for juvenile myelomonocytic leukaemia" and "Terapia avanzada CAR-T CD19/CD22", Ayuda Nominativa de la Consejería de Investigación, Comunidad de Madrid, Spain. Work in MI lab was funded by a grant from the Spanish Ministry of Science and Innovation (PID2020-114148RB-I00). VGG was granted with Río Hortega (AES 2022 exp. Nº. CM22/00078) and Juan Rodés (AES 2024 exp. Nº. JR24/00003) contracts from the Carlos III Health Institute (ISCIII) through the European Funds of the Recovery, Transformation and Resilience Plan and financed by the European Union NextGenerationEU.
González‐Martínez et al. (Fri,) studied this question.