CPX-351 Liposome in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia


Key Points

  • CPX-351 improved overall survival vs standard cytarabine plus daunorubicin.
  • The CPX safety profile was similar to that of standard therapy.

In a pivotal phase III trial reported in the Journal of Clinical Oncology, Lancet et al found that cytarabine and daunorubicin liposome (CPX-351, Vyxeos) significantly improved overall survival vs standard cytarabine plus daunorubicin (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). The study supported the approval of CPX-351 for treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes in September 2017.

Study Details

In the open-label trial, 309 patients aged 60 to 75 years with newly diagnosed high-risk/sAML enrolled between December 2012 and November 2014 at 39 sites in the United States and Canada were randomized to receive one to two induction cycles of CPX-351 (n = 153) or 7+3 (n = 156) followed by consolidation therapy with a similar regimen. The initial CPX-351 induction course consisted of 100 units/m2 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) via 90-minute infusion on days 1, 3, and 5. The initial 7+3 induction course consisted of cytarabine 100 mg/m2/d via 7-day continuous infusion with daunorubicin 60 mg/m2 on days 1 to 3.

The primary endpoint was overall survival.

Overall Survival

Median follow-up was 20.7 months. Median overall survival was 9.56 months in the CPX-351 group vs 5.95 months in the 7+3 group (hazard ratio [HR] = 0.69, P = .003). Estimated overall survival was 41.5% vs 27.6% at 1 year and 31.1% vs 12.3% at 2 years. Benefit of CPX-351 was observed across AML subtypes and age in prespecified subgroup analyses. Overall remission rates were 47.7% vs 33.3% (P = .016). Median event-free survival was 2.53 vs 1.31 months (HR = 0.74, P = .021).


The incidence of nonhematologic adverse events were similar in the two groups. The CPX-351 group had a longer treatment phase and prolonged time to neutrophil (median 35 vs 29 days) and platelet count (36.5 vs 29 days) recovery. The most common grade ≥ 3 adverse events in the CPX-351 group were febrile neutropenia (68.0% vs 70.9%), pneumonia (19.6% vs 14.6%), and hypoxia (13.1% vs 15.2%). Early mortality rates with CPX-351 vs 7+3 were 5.9% vs 10.6% (P = .149) through day 30 and 13.7% vs 21.2% (P = .097) through day 60.

The investigators concluded, “CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.”

The study was supported by Celator Pharmaceuticals, a subsidiary of Jazz Pharmaceuticals.

Jeffrey E. Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.