VYSION (VYxeoS liposomal® Italian Observational study iN the real practice): Study design and baseline characteristics

Abstract

Abstract CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, was approved for newly diagnosed (ND) therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) following favorable efficacy and safety from the pivotal phase 3 trial. While clinical trials provide critical insights into the efficacy and safety of novel therapies, their controlled environments and strict criteria can limit generalizability. To provide further insight into the real-world use of CPX-351, VYSION aims to evaluate the effectiveness and safety of CPX-351 in adults with t-AML or AML-MRC receiving CPX-351 as part of their normal clinical care. VYSION is the first prospective, single-arm, non-experimental, observational study of CPX-351. Inclusion criteria comprise adults (≥18 years) with ND t-AML or AML-MRC (per the 2016 WHO classification) initiating treatment with CPX-351 in their normal clinical practice and considered eligible for intensive chemotherapy in the treating physician's opinion. The decision to prescribe CPX-351 treatment must have been made prior to and regardless of enrollment in the study. The primary outcome is the percentage of patients who achieve CR/CRi/CRh without measurable residual disease (MRD) at the end of treatment (i.e., last response evaluation after the last treatment cycle), assessed per the 2022 European LeukemiaNet (ELN) response criteria. Bone marrow samples will be assessed locally for MRD via multiparameter flow cytometry (MFC), with MRD negativity defined as <10-3 per the 2021 ELN guidelines. Secondary outcomes include overall response rate (CR+CRi+CRh) after induction phase; CR/CRi/CRh rate without MRD post-induction and pre-transplantation; OS from CPX-351 treatment initiation date; hematopoietic cell transplantation (HCT) rate; OS landmarked from HCT date; safety; and patient fitness status (per Ferrara criteria) before HCT and at the final treatment visit for patients ineligible for HCT. Change in patient reported outcomes during treatment and healthcare resource utilization will also be explored. All enrolled patients will be observed until the last enrolled patient still alive has been followed for 12 months. At data cutoff (May 16, 2025), VYSION has enrolled 112 patients and 106 were included in this analysis of baseline patient characteristics: 21% (n=22) had t-AML and 79% (n=84) had AML-MRC. Of those with AML-MRC, 40% (n=34) had history of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasms (MPN), 35% (n=29) had an MDS-related cytogenetic abnormality, and 42% (n=35) had multilineage dysplasia. Among patients with history of MDS or MDS/MPN and available data on prior therapy, 58% (11/19) received prior hypomethylating agents. Overall, median age was 68 years (IQR: 61-71); 20% (n=21) of patients were <60 years. Most patients were male (58% [n=62]) and White (95% [n=101]); all with available Eastern Cooperative Oncology Group performance status data had a score of 0-1 (100% [n=101]). Comorbidities were common and 42% (n=44) of patients had ≥3 ongoing comorbidities. Of patients with available cytogenetic data, 57% (59/103) had an abnormal karyotype. Of patients screened for gene mutations, 21% (20/97) had mutated TP53 and 35% (34/97) had ≥1 MDS-related gene mutation. In total, 65% (68/104) of patients were classified as adverse risk per 2022 ELN. Of patients assessed for transplantation eligibility, 96% (75/78) were eligible. Ferrara criteria assessment for fitness evaluation was performed in 83% (88/106) of patients. Overall, 94% (100/106) of patients were considered eligible for intensive chemotherapy in the investigator's opinion. In patients assessed by the EORTC QLQ-C30 with available data, mean global health status was 54 (SD: 22.9; n=99) and mean physical functioning score was 78 (SD: 20.1; n=101). VYSION is ongoing with study closure anticipated in October 2025. As the first prospective observational study of CPX-351, VYSION directly collects data during patient treatment, enhancing the clinical significance of the findings. Furthermore, this prospective design uniquely enables the collection of quality-of-life data and the standardized assessment of CPX-351's impact on MRD via MFC at key timepoints. VYSION has the potential to provide valuable insights into effectiveness and safety of CPX-351 in routine clinical practice. ClinicalTrials.gov ID: NCT06143839.