Real-World Data Confirms CPX-351 Efficacy and Safety for Newly Diagnosed t-AML and AML-MRC, With Enhanced Outcomes in Younger Patients and MR-Mutated Disease
In the retrospective, multicenter Vyxeos Real-world US Long-term Effectiveness and Safety Study (V-RULES) study, CPX-351 demonstrated real-world effectiveness and safety among. patients with newly diagnosed (ND) therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC).
These data were presented by Thomas LeBlanc, MD, Duke University School of Medicine, Durham, North Carolina, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
Among 161 patients treated with CPX-351, 47 were diagnosed with t-AML and 114 with AML-MRC. The median age at diagnosis was 60 years (range, 21 to 78) and 48% of patients were over the age of 60 years. Most patients received 1 cycle of CPX-351 (n = 142) and 19 received 2 cycles. Over half of patients (63%) had myelodysplasia-related gene mutations (MRm) and 25% had TP53 mutations (TP53m).
The median time to follow-up was 9.7 months (interquartile range [IQR], 4.1 to 27.8). The overall composite remission rate was 63% among 149 evaluable patients, of which 85% of patients who achieved CR had t-AML and 53% had AML-MRC.
The median overall survival (OS) was 12.9 months (95% confidence interval [CI], 8.9 to 19.7), with an estimated 4-year OS of 29% (95% CI, 21–38%). Patients less than 60 years of age had a longer median OS (17.8 vs 10.6 months) and higher estimated 4-year OS (37% vs 22%) compared to patients over 60 years of age.
Patients with myelodysplasia-related gene mutations (MRm) had prolonged survival (median OS 17.8 month; 11.4 to 38), while those with TP53 mutations had a shorter OS (median OS 5.3 months; 95% CI, 2.3 to 7.4).
Among treated patients, 38% proceeded to hematopoietic cell transplantation (HCT) following CPX-351, and the median OS post-HCT OS was 45.6 months (95% CI, 24.9 to not estimated). The median time to hematologic recovery among responders was 35 days for neutrophils and 36 days for platelets.
In terms of safety, the most common grade ≥3 adverse events included infection (52%) and febrile neutropenia (42%).
“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,” the researchers concluded. “Notably, this study demonstrated favorable outcomes for younger patients (<60 years) who were not included in the pivotal trial.”
Source:
LeBlanc T, Lai C, Ali A, et al. V-RULES: Real-world effectiveness and safety of CPX-351 in patients with secondary acute myeloid leukemia (AML). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 6520.
