P054 | THE GIMEMA ALL2720 STUDY EXPLORES THE FEASIBILITY OF INTEGRATING DRUG RESPONSE PROFILING WITH GENOMIC ANALYSES TO GUIDE TREATMENT DECISIONS IN R/R T-ALL AND ETP-ALL

Introduction Relapsed/refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) and early T-cell precursor ALL (ETP-ALL) have a poor prognosis and limited therapeutic options. Given the urgent need for more effective treatments, we designed the GIMEMA ALL2720 trial with the aim of providing a personalized therapy to these high-risk T-ALL patients by analyzing leukemia cells with a combined Drug response profiling (DRP) and molecular/cytogenetic approach. In the present report, we evaluated the feasibility of this approach. Methods Protocol enrollment lasted 3 years (May 2021-June 2024) and involved 15 GIMEMA centers. Bone marrow and/or peripheral blood samples were collected and shipped simultaneously to 2 reference laboratories located in Perugia and Parma to guarantee a homogeneous assessment. Evaluable samples underwent combined interphase (CI)-FISH, SNP array, NGS analyses, and ex vivo DRP, including a panel of 77 small molecules. A drug sensitivity score was derived from DRP. Two reports, one on genomics and one on DRP results, were delivered and discussed with the treating physicians. Therapeutic choice was left to the physician and depended on medical needs and availability of targeted drugs. Results The samples of the 32 eligible patients were sent for evaluation to the reference laboratories that received them within 24 hours from shipment. Of them, 3 cases (9.3%) were not evaluable: 1 was not shipped according to guidelines and 2 were hypocellular. The cohort of 29 evaluable samples included 21 ETP-ALL (14 R/R and 7 at diagnosis) and 8 R/R T-ALL. All of them were successfully evaluated by CI-FISH/SNPa and 28 also by NGS and DRP. Results of the genomic evaluation and DRP were delivered within a median of 7 days (range 4-15) and treatment recommendations were made available for 28/29 (96.5%) of patients. It was possible to identify a median of 16 active compounds per sample (range 2-33). Importantly, 15/28 patients (53.6%) – including 12 ETP-ALL - received a pharmacogenomic-matched treatment, with 4 also able to undergo transplantation. Discussion The ALL2720 study represents a proof-of-principle of the feasibility of timely transfer laboratory results to patients’ bedside. Indeed, roughly 90% of high-risk T-ALL patients benefited from an avant-garde integrated pharmacogenomic characterization of their disease. More than 50% of patients received tailored treatments, including bone marrow transplantation, that otherwise would have been precluded.