CPX-351 Before Transplant Improves Survival for Older Patients With AML

An exploratory subgroup analysis of older patients with high-risk acute myeloid leukemia who took the liposomal formulation CPX-351 (Vyxeos) before allogeneic hematopoietic cell transplantation demonstrated that the drug improves overall survival and reduces the risk of early death.

Jeffrey E. Lancet, MD

An exploratory subgroup analysis of older patients with high-risk acute myeloid leukemia (AML) who took the liposomal formulation CPX-351 (Vyxeos) before allogeneic hematopoietic cell transplantation (HCT) demonstrated that the drug improves overall survival (OS) and reduces the risk of early death, suggesting that the formulation may provide a bridge to successful transplantation in a population with limited treatment options and poor survival rates.


Jeffrey E. Lancet, MD, senior member and chief of the Leukemia/Myelodysplasia Program at the Moffitt Cancer Center, presented this new subgroup analysis during a press conference at the 2016 ASH Annual Meeting.

CPX-351 is a liposomal formulation containing a fixed combination of cytarabine and daunorubicin in a 5:1 molar concentration ratio within the liposome using a system known as “CombiPlex,” which was developed by Celator. “The beauty of [this approach],” Lancet explained, “is that the drugs together are delivered in a synergistic ratio that optimizes leukemic cell kill.”

The originator study from which these subgroup data were drawn, was carried out between December 2012 and November 2014 across 39 sites in the United States and Canada. This open-label, randomized, prospective phase III trial compared CPX-351 induction chemotherapy with cytarabine plus daunorubicin in 309 high-risk patients between the ages of 60 and 75 with newly diagnosed secondary AML. These high-risk patients included those whose AML arose from myelodysplastic syndrome (MDS) or whose disease had MDS-related cytogenetic abnormalities, as well as those whose AML was related to prior chemotherapy.





Patients were randomized 1:1 to an experimental arm receiving an induction of 100 units/mof CPX-351 on days 1, 3, and 5, or a control group receiving cytarabine 100 mg/mfor 7 days, followed by daunorubicin 60 mg/mon days 1, 2, and 3 (“7+3” regimen). At 12 months, 41.5% of patients enrolled in the CPX-351 arm remained alive versus 27.6% in the 7+3 arm. At 24 months, 31.1% of patients enrolled in the CPX-351 arm of the study remained alive, compared with 12.3% with 7+3, according to findings presented at the 2016 ASCO Annual Meeting.

The subgroup analysis presented at ASH focused on the one-third of patients in the phase III study cohort who went on to have allogeneic HCT, 52 of whom had received the CPX-351 therapy and 39 the 7+3 regimen.

“We were interested in understanding what the contribution of allogeneic transplant was to the overall efficacy of CPX-351,” said Lancet in explaining the rationale for the study. He added that the two HCT cohorts were well-matched on baseline characteristics, although a higher percentage of patients were in complete remission if they had received CPX-351 before undergoing transplant.

Investigators compared median OS at the time of allogenic transplant and found that patients who had received CPX-351 lived longer than patients who received 7+3; OS was not reached in the experimental arm and was 10.25 months for the control group (HR, 0.46;P= .0046).

Mortality 100 days after transplant was also lower in the CPX-351 group: 9.6% for patients in the CPX-351 arm versus 20.5% in the 7+3 arm—equivalent to 53% fewer deaths among patients receiving CPX-351.

Lancet noted that these results are from a nonrandomized subgroup and should be interpreted with caution. Nevertheless, he said the findings point to superior outcomes after allogenic transplant among older patients with high-risk AML given CPX-351 beforehand.

Although Lancet said that the results still need to be verified, “Lower induction-related morbidity and mortality could reflect a healthier patient population going into transplant who received CPX-351 and possibly a better opportunity to achieve disease control before moving into transplant.”

Harry P. Erba, MD, PhD, a professor of medicine and director of the UAB Hematology Malignancy Program, described these findings as not only “statistically significant, but I and many of my colleagues find it to represent a clinically significant difference in overall survival,” suggesting that the encapsulated formulation adds real benefit for this subgroup of difficult-to-treat patients.

The FDA granted fast track status to CPX-351 in January 2015 for the treatment of elderly patients with secondary AML based on phase II data, and in May 2016, the agency gave the drug a breakthrough designation based on the results of the overall phase III trial. “Moving forward, I believe that this CPX-351 will receive an indication as frontline therapy for patients in whom the benefit was achieved,” Lancet predicted.

He added that there is interest in developing CPX-351 in younger patients with similar biologic features, such as adverse karyotype or an adverse mutational profile, and in the “non—high risk patients,” where a clear benefit has not been observed with the drug thus far.


  1. Lancet JE, Hoering A, UY GL, et al. Survival following allogeneic hematopoietic cell transplantation in older high-risk acute myeloid leukemia patients initially treated with CPX-351 liposome injection versus standard cytarabine and daunorubicin: subgroup analysis of a large phase III trial. Presented at: 58th American Society of Hematology Annual Meeting; San Diego, CA; December 3-6, 2016. Abstract 906.
  2. Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of cpx-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML.J Clin Oncol34, 2016 (suppl; abstr 7000).