Advancing chemogenomic strategies for functional precision medicine in relapsed-refractory T-ALL and ETP-ALL: the GIMEMA ALL2720 trial

Despite the vast amount of cancer genomic data, linking mutations to drug efficacy remains challenging. National efforts integrating ex vivo drug response profiling (DRP) with clinical genomics are rare. To address this gap, we designed the GIMEMA ALL2720 trial (NCT04582487), a multicenter study evaluating a chemogenomic approach in T-cell acute lymphoblastic leukemia (T-ALL), a subtype still lacking effective salvage therapies. 29 patients with de novo or relapsed/refractory (R/R) T-ALL or ETP-ALL were enrolled in the study to receive genomic profiling and DRP. Integrated patient-specific reports were generated within a median of 7 days. DRP revealed recurrent vulnerabilities and four response clusters. Of 28 fully profiled patients, 15 (53.6%) received chemogenomic-guided therapy, achieving a complete remission rate of 46.7%. Four responders proceeded to transplantation. This prospective study demonstrates the nationwide feasibility and clinical relevance of integrating genomic and ex vivo DRP in T-ALL, supporting functional-guided precision medicine as a promising strategy to broaden salvage options and improve outcomes.