CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 713 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 713. These exploratory post hoc subgroup analyses evaluated the impact of achieving complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) with CPX-351 (73/153 [48%]) vs conventional 713 (52/56 [33%]) on outcomes. CPX-351 improved median OS vs 713 in patients who achieved CR or CRi (25.43 vs 10.41 months; hazard ratio 5 0.49; 95% confidence interval, 0.31, 0.77). Improved median OS was seen across AML subtypes (t-AML, AML-MRC), age subgroups (60 to 69 vs 70 to 75 years), patients with prior hypomethylating agent exposure, and patients who did not undergo transplantation. Patients who achieved CR or CRi with CPX-351 also had a higher rate of transplantation, a longer median OS landmarked from the date of transplantation (not reached vs 11.65 months; hazard ratio 5 0.43; 95% confidence interval, 0.21, 0.89), and a safety profile that was consistent with the known safety profile of 713. These results suggest deeper remissions may be achieved with CPX-351, leading to improved OS. This study was registered at www.clinicaltrials.gov as #NCT01696084.
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