Bridging therapy in pediatric and AYA patients under 25 years with relapsed/refractory B-ALL undergoing anti-CD19 CAR-T therapy: a multicenter retrospective study by the Spanish group GETH-TC

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Abstract
CAR-T therapy is a powerful treatment for pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, the impact of bridging therapy prior to CAR-T infusion on patient outcomes remains insufficiently explored. In this retrospective study of patients with relapse/refractory B-ALL (N = 103), we compared outcomes across different bridging therapy groups: Low-Intensity Chemotherapy (LIC, N = 50), Immunotherapy (N = 20), or High-Intensity Chemotherapy (HIC, N = 33). At day +28 post-infusion, LIC and Immunotherapy showed significantly higher rates of Complete Remission with negative Minimal Residual Disease compared with HIC (96% vs 85% vs 75%), along with lower rates of disease progression (4% vs 10% vs 15.2%) and treatment-related mortality (0% vs 5% vs 9.1%). Additionally, patients who received three or more prior lines of therapy before CAR-T infusion exhibited significantly lower response rates. Despite potential biases, such as intrinsic disease aggressiveness or unidentified genomic alterations, present findings suggest that using LIC or immunotherapy as bridging strategies, in patients with fewer prior treatment lines, may be associated with a lower overall disease and treatment burden and could potentially contribute to improved CAR-T cell efficacy and clinical outcomes. Nevertheless, additional investigations are required to elucidate biological and clinical mechanisms by which bridging approaches and treatment history modulate CAR-T responses.

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