Impact of fitness categorization according to SIE/SIES/GITMO criteria in therapy-related and AML-MRC receiving CPX-351

CPX-351, a novel liposomal formulation of cytarabine and daunorubicine, represents the standard of care in fit patients with myelodysplasia-related changes (AML-MRC) and therapy-related Acute Myeloid Leukemia (tAML). Considering its better safety profile than conventional intensive chemotherapy, we investigated its cost/benefit ratio, in terms of overall survival and of mortality, in a large multicentric series of AML-MRC and tAML receiving CPX-351 outside clinical trials between 2019 and 2022. Patients were classified in fit or unfit to intensive chemotherapy through a comprehensive evaluation of age, comorbidities and performance status by adopting SIE/SIES/GITMO criteria. Disease risk was defined according to the ELN2017 classification. Before treatment start, 328/403 (81.4%) were classified as fit, 75/403 (18.6%) as unfit. Three hundred and ninety-six had a full genetic/cytogenetic profile with 17 (4%) being categorized as favorable risk, 162 (41%) intermediate risk, and 217 (55%) adverse risk according to ELN2017. After induction, 230/403 patients (57.1%) achieved a complete remission, with no differences between fit (57.3%) and unfit (56%). However, the two groups significantly differed in terms of survival (median overall survival of 18 months vs 8 months for fit and unfit patients) and of 28- and 100-day mortality (4.6% vs 10.7% at 28 days and 14.3% vs 32% at 100-days for fit and unfit patients, respectively). In conclusion, the SIE/SIES/GITMO criteria discriminated patient subgroups with different short- and long-term outcomes after treatment with CPX-351. The update or design of dedicated fitness criteria could represent a future and valid strategy to optimize the use of this specific treatment.