Background: Favorable survival outcomes with CPX-351 vs conventional 7 + 3 and comparable safety in adults aged 60–75 years in the pivotal phase 3 trial (NCT01696084) led to the approval of CPX-351 for newly diagnosed therapy-related acute myeloid leukemia (tAML) or AML with myelodysplasia-related changes (AML MRC) in the US and Europe. However, the trial did not include patients aged <60 years, creating a data gap on the potential effectiveness in younger patients. The CPX-351 Real-world Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine UK clinical practice in patients aged ≥18 years with newly diagnosed tAML or AML MRC. Aims: We report the results of a post-hoc analysis of the CREST-UK study to provide insight into the effectiveness and safety of CPX-351 in patients aged <60 vs ≥60 years with tAML or AML MRC. Methods: CREST-UK was a retrospective, noninterventional, multicenter, single-arm, observational study. Pseudonymized data were collected from the medical records of adults (aged ≥18 years) with newly diagnosed tAML or AML MRC (per WHO 2016 criteria) who received ≥1 infusion of CPX-351. Primary outcomes were overall survival (OS) and complete remission (CR)/CR with incomplete platelet or neutrophil recovery (CRi). Effectiveness and safety outcomes were compared between patients aged <60 and ≥60 years. Results: In total, 147 patients received first induction of CPX-351 (<60 years, 38%; age range: 18–59 years vs ≥60 years, 62%; age range: 60–83 years). Most patients (76%) had a diagnosis of AML MRC (70% [<60 years] vs 80% [≥60 years]); prior myelodysplastic syndrome ([MDS] 46% vs 34%) and MDS-related cytogenetic abnormalities (36% vs 37%) were the two most common subtypes. Cytogenetic/molecular characteristics in patients aged <60 vs ≥60 years were normal karyotype (30% vs 38%), complex or monosomal karyotype, -17, or abn(17p) (23% vs 24%); adverse genetic risk per 2017 ELN criteria was reported in 50% vs 46%. Prior azacitidine exposure was reported in 9% of patients (2% vs 13%). Estimated median OS was longer in the <60 years cohort (20.0 months) vs the ≥60 cohort (9.9 months [Figure 1A]). For patients <60 years, 3-year OS was 42% and 30-day all-cause mortality was 5%; these were 29% and 8% for those ≥60 years. Overall, 34% of patients received hematopoietic cell transplantation (HCT) during the study period (52% [<60 years] vs 23% [≥60 years]); median OS post-HCT was not reached in either age group (Figure 1B). Based on best response, CR/CRi rates were higher in evaluable patients (n=138) aged <60 years (66%) than those ≥60 years (44%). In multivariable analyses, older age (in decades) was associated with reduced OS (hazard ratio 1.43, p=0.017) but not achievement of CR/CRi. In patients aged <60 vs ≥60 years who achieved CR/CRi after first induction, the median time to neutrophil recovery was 33.5 days (n=30) vs 33.0 days (n=34), respectively; for platelet recovery, these were 34.0 days (n=27) vs 36.0 days (n=33). Overall, 39% of patients experienced a serious TEAE (38% [<60 years] vs 40% [≥60 years]); 75% of patients had a Grade ≥3 TEAE (71% vs 77%). Febrile neutropenia (38%) was the most common Grade ≥3 TEAE (45% vs 34%). The overall incidence of all cardiac TEAEs was 11% (16% vs 8%). Summary/Conclusion: These results suggest that CPX-351 demonstrated clinical effectiveness and a tolerable safety profile in adults with AML aged <60 and ≥60 years, consistent with the phase 3 trial data. Interestingly, 3-year OS was longer in younger patients, likely due to a higher transplant rate, with median OS post-HCT not reached in both age groups.Keywords: Age, Acute myeloid leukemia, Cytarabine, Chemotherapy