Study Compares Adverse Event Profile for CPX-351 and Conventional 7+3 for AML

December 09, 2017

CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. In a randomized, phase III study, researchers evaluated induction therapy with CPX-351 versus conventional cytarabine/daunorubicin (referred to as 7+3 regimen) in adults aged 60–75 years with newly diagnosed, treatment-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes. Bruno C Medeiros, MD, at Stanford University School of Medicine in California, discussed the findings at the ASH Annual Meeting (

Patients were randomized 1:1 to receive one to two cycles of CPX-351 100 units/m2 (including 100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) on days one, three, and five (days one and three for second induction) or conventional 7+3 (given as cytarabine 100 mg/m2 daily for seven days [five days for second induction] and daunorubicin 60 mg/m2 on days one through three [days one and two for second induction]). Patients who reached complete response (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to two consolidation cycles. A total of 309 patients were included: 153 received CPX-351 and 156 received 7+3.

The researchers presented an analysis of adverse events (AEs) in each group (this did not include AEs that occurred after hematopoietic cell transplantation [HCT]).

Patients treated with CPX-351 had significantly prolonged median overall survival (the study’s primary endpoint) compared to those treated with 7+3 (9.56 versus 5.95 months; hazard ratio = 0.69; 95% CI = 0.52–0.90; p = 0.005). CPX-351 also resulted in a significantly higher CR+CRi rate compared to 7+3 (48% versus 33%; p = 0.016). A greater proportion of patients could undergo HCT in the CPX-351 cohort (34% versus 25%).

Safety outcomes were evaluable for 153 patients in the CPX-351 group and 151 patients in the 7+3 cohort. The proportion of patients who experienced AEs was seemingly comparable between the two groups; however, a greater proportion of patients in the CPX-351 arm received first and second consolidation (32% and 15%, respectively) than the 7+3 arm (21% and 8%, respectively), which resulted in a longer median duration of the treatment phase with CPX-351 (62 days) compared to the 7+3 arm (41 days). This leads to a longer AE reporting period for the CPX-351 cohort, the researchers noted.

To compensate for this difference in treatment duration, the researchers calculated the rate of AEs per patient-year (reported from the first dose date through 30 days after the end date of the treatment phase). They found that the rates of AEs per patient-year and early mortality were lower with CPX-351 than with conventional 7+3.

The median rate of AEs per patient-year was 75.68 (range = 10.4–243.5) in the CPX-351 arm and 87.22 (range = 11.1–248.4) in the 7+3 arm. The median rate of AEs per patient-year among patients who achieved a CR+CRi was 62.97 (range = 18.3–175.7) in the CPX-351 arm and 74.38 (range = 29.2–159.1) in the 7+3 arm. The median rate of grade ≥3 AEs per patient-year was 12.24 (range = 0.0–79.7) with CPX-351 and 13.53 (range = 0.0–116.9) with 7+3.

The median rate of serious AEs per patient-year was higher in the CPX-351 arm (3.15, range = 0.0–36.5 versus 0, range = 0.0–31.0). “This may be due, in part, to a greater proportion of patients in the CPX-351 arm receiving consolidation therapy in an outpatient setting (51% of patients in cycle one and 61% in cycle two) compared to the 7+3 arm (6% and 0%, respectively), as, for these patients, management of AEs may have required a move to a hospital setting, which is one of the criteria for classifying an AE as a serious AE,” the researchers noted.

The most frequently reported serious AEs in the CPX-351 and 7+3 cohorts were febrile neutropenia (8% and 5%), respiratory failure (7% and 5%), decreased ejection fraction (6% and 6%), sepsis (8% and 3%), and pneumonia (7% and 4%). Early mortality rates were lower for patients receiving CPX-351 versus 7+3 at both 30 (5.9% versus 10.6%) and 60 days (13.8% versus 21.2%).

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