Background
Phase III RCT (n=309), 60-75 years, newly diagnosed secondary AML (t-AML and AML-MRC). Patients received 1-2 induction cycles of CPX-351 (liposomal daunorubicin/cytarabine, fixed 5:1 molar ratio) or 7+3, followed by consolidation.
Interventions and follow up
Arm A (CPX-351): First induction 100 U/m2 (90-min IV) on days 1, 3, 5; second induction 100 U/m2 on days 1, 3; consolidation 65 U/m2 on days 1, 3.
Arm B (7+3): First induction cytarabine 100 mg/m2/d CIV days 1-7 + daunorubicin 60 mg/m2 days 1-3; second induction 5+2; consolidation 5+2.
Primary endpoint: OS
Median follow-up: 20.7 mo
Arm B (7+3): First induction cytarabine 100 mg/m2/d CIV days 1-7 + daunorubicin 60 mg/m2 days 1-3; second induction 5+2; consolidation 5+2.
Primary endpoint: OS
Median follow-up: 20.7 mo
Results
mOS: 9.6 vs 5.9 mo (A vs B); HR 0.69, 95%CI 0.52-0.90, P=.003
1-yr OS: 42% vs 28%
2-yr OS: 26% vs 13%
CR + CRi: 47.7% vs 33.3%, P=.016
CR: 37.3% vs 25.6%, P=.040
CR + CRi (1 induction): 55.2% vs 34.0%
CR + CRi (2 inductions): 31.3% vs 35.3%
mEFS: 2.53 vs 1.31 mo, HR 0.74, 95%CI 0.58-0.96, P=.021
1-yr OS: 42% vs 28%
2-yr OS: 26% vs 13%
CR + CRi: 47.7% vs 33.3%, P=.016
CR: 37.3% vs 25.6%, P=.040
CR + CRi (1 induction): 55.2% vs 34.0%
CR + CRi (2 inductions): 31.3% vs 35.3%
mEFS: 2.53 vs 1.31 mo, HR 0.74, 95%CI 0.58-0.96, P=.021
Adverse events
Hematologic/cytopenias: Grade 1-5 hemorrhagic events 74% vs 56% (A vs B); prolonged cytopenias with CPX-351.
Infections: Febrile neutropenia 68.0% vs 69.5%; pneumonia 18.3% vs 17.2%; bacteremia 7.8% vs 2.7%.
Other grade ≥3: Respiratory failure 7.2% vs 5.3%; decreased ejection fraction 5.9% vs 6.0%.
Mortality: 60-day all-cause mortality 13.7% vs 21.2%.
Infections: Febrile neutropenia 68.0% vs 69.5%; pneumonia 18.3% vs 17.2%; bacteremia 7.8% vs 2.7%.
Other grade ≥3: Respiratory failure 7.2% vs 5.3%; decreased ejection fraction 5.9% vs 6.0%.
Mortality: 60-day all-cause mortality 13.7% vs 21.2%.
Conclusions
CPX-351 significantly improved median OS and remission rate versus 7+3 in patients 60-75 years with newly diagnosed secondary AML (t-AML/AML-MRC).
Key Limitations
Restricted to older adults (60-75) with secondary AML; not generalizable to de novo or younger AML. Open-label design. Limited molecular subgroup characterization. Comparator was conventional 7+3 without modern targeted agents.
Clinical Context
FDA-approved (2017) and EMA-approved for newly diagnosed t-AML or AML-MRC in adults. Endorsed by ELN/ASCO frameworks as a preferred intensive induction option for fit older patients with secondary AML; CPX-351 responders may bridge to allogeneic HCT.