V-RULES: Real-world effectiveness and safety of CPX-351 in patients with secondary acute myeloid leukemia (AML).

6520 Background: CPX-351 was approved for newly diagnosed (ND) therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) following the pivotal phase 3 trial, which demonstrated improved CR/CRi (47.7% vs 33.3%) and median OS (9.56 vs 5.95 months [mo]), and comparable safety vs conventional 7+3 in adults aged 60-75 years. The Vyxeos Real-world US Long-term Effectiveness and Safety Study (V-RULES) evaluated real-world (RW) clinical outcomes and safety of CPX-351 in US patients with ND t-AML or AML-MRC. Methods: V-RULES is a retrospective, multicenter, single-arm study based on medical records of patients with ND t-AML or AML-MRC who were treated with CPX-351 since its FDA approval in August 2017. Primary endpoints were CR/CRi/CRh and OS. Results: Overall, 161 patients (t-AML, n=47; AML-MRC, n=114) received ≥ 1 induction of CPX-351 (1 cycle, n=142; 2 cycles, n=19) and 50 patients received consolidation (1 cycle, n=40; 2 cycles, n=10). Median age at AML diagnosis was 60 years (range: 21-78); 78 (48%) patients were aged <60 years. Of patients with available cytogenetic data, 88/154 (57%) were classified as adverse-risk per Grimwade 2010 and 49/155 (32%) had complex karyotype. Notably, 33/134 patients (25%) had TP53 mutations ( TP53 m) and 57/91 patients (63%) had myelodysplasia-related gene mutations (MRm). Median follow-up time (IQR) was 9.7 mo (4.1, 27.8). CR (including minimal residual disease negativity)/CRi/CRh at any time was 63% in 149 evaluable patients (t-AML, 85%; AML-MRC, 53%). Median OS was 12.9 mo (95% CI: 8.9, 19.7) and estimated 4-year OS was 29% (95% CI: 21%, 38%). Survival was longer in patients aged <60 vs ≥ 60 years: median OS was 17.8 (95% CI: 9.6, 45.4) vs 10.6 mo (95% CI: 6.7, 13.8) and estimated 4-year OS was 37% (95% CI: 24%, 49%) vs 22% (95% CI: 12%, 34%). Compared with the overall population, median OS was shorter in patients with TP53 m (5.3 mo [95% CI: 2.3, 7.4]) and longer in patients with MRm (17.8 mo [95% CI: 11.4, 38]). Patients who underwent hematopoietic cell transplantation (HCT) after CPX-351 treatment (38%) had a median OS post-HCT of 45.6 mo (95% CI: 24.9, not estimated). In patients with CR/CRh/CRi, median time to neutrophil (≥ 500/μL) and platelet (≥ 50,000/μL) recovery in induction 1 was 35 days (n=76) and 36 days (n=72), respectively. Infection (52%) and febrile neutropenia (42%) were the most common grade ≥ 3 adverse events (AEs); 2 patients had a serious AE of cardiac events. Conclusions: These results highlight the effectiveness and safety of CPX-351 for the treatment of t-AML and AML-MRC in the US RW setting, consistent with the pivotal trial and published RW data. Notably, this study demonstrated favorable outcomes for younger patients (<60 years) who were not included in the pivotal trial. Patients who received HCT also had improved outcomes, as did those with MRm. These results support the continued use of CPX-351 as the standard of care for ND t-AML or AML-MRC.