CPX-351 Continues to Improve OS in High-Risk AML Subtypes


February 10, 2021 - CPX-351 demonstrated improved overall survival at 5 years versus standard 7+3 chemotherapy in older patients with newly diagnosed high-risk or secondary acute myeloid leukemia.

Jorge E. Cortes, MD

Jorge E. Cortes, MD

CPX-351 (Vyxeos) demonstrated improved overall survival (OS) at 5 years versus standard 7+3 chemotherapy in older patients with newly diagnosed, high-risk or secondary acute myeloid leukemia (AML) who achieved a complete response (CR) or a CR with incomplete hematologic recovery (CRi), or who underwent hematopoietic stem cell transplant (HCT), according to findings from the phase 3 CLTR0310-301 trial, which were presented at the 2021 Transplant and Cellular Therapy Meeting.1

In the study, patients were randomized 1:1 to CPX-351 (n = 153)—a dual-drug encapsulation of cytarabine/daunorubicin—or the 7 + 3 regimen (n = 156), defined as the combination of cytarabine and daunorubicin.

“The longer OS with CPX-351 versus 7 + 3 in patients who achieved CR or CRi and in those who underwent HCT suggests potentially deeper responses may be achieved with CPX-351 treatment,” the authors of the poster, who were led by Jorge E. Cortes, MD, wrote in their conclusion. “These data support the prior evidence that CPX-351 has the ability to produce and contribute to long-term remission and survival in older patients with newly diagnosed high-risk/secondary AML.”

In the total cohort, patients receiving CPX-351 experienced a median OS of 9.33 month (95% CI, 6.37-11.86) compared with 5.95 months (95% CI, 4.99-7.75) in patients who were treated with the standard comparator (HR, 0.70; 95% CI, 0.55-0.91). OS rates at 3 (21% vs 9%) and 5 years (18% vs 8%) were both superior in the CPX-351 arm.

HCT was received by 53 patients from the CPX-351 arm and 39 patients from the 7 + 3 arm; the median OS landmarked from the date of HCT in these patients was not reached versus 10.25 months, respectively (HR, 0.51; 95% CI, 0.28-0.90). The corresponding rates of survival at 3 years were 56% and 23%.

In all patients achieving a CR or CRi in the CPX-351 (n = 73) and the 7 + 3 (n = 52), the median OS was better for those in the experimental arm at 21.72 months versus 10.41 months, respectively (HR, 0.59; 95% CI, 0.39-0.88). Rates of OS at 3 and 5 years in the CPX-351 group were 36% and 30% compared with 23% and 19% with the 7 + 3 regimen. The risk of disease progression or death improved further with CPX-351 in this group when patients subsequently underwent HCT (HR, 0.50; 95% CI, 0.26-0.97).

By age group, the survival advantage of CPX-351 over 7 + 3 was most notable in patients aged 70 to 75 years, with a corresponding median of 8.87 months and 5.62 months (HR, 0.52; 95% CI, 0.34-0.77). Estimated 3- and 5-year survival rates with CPX-351 were 18% and 16%, respectively, versus 0% for both timepoints in patients receiving 7 + 3. Survival advantage was also noted in those ages 60 to 69 years, yet the advantage in the risk of disease progression or death was lower (HR, 0.73; 95% CI, 0.54-0.99).

In the CPX-351 and 7 + 3 arms, there were a total of 124 and 140 deaths, respectively, from progressive leukemia (56% vs 53%) and adverse events (14% each), among other causes. The safety profile of the experimental regimen was generally consistent with the known safety profile of conventional 7 + 3 therapy. All-cause and early mortality rates (30- and 60-day) were lower with CPX-351.

When patients were stratified by ECOG performance status, disease karyotype, and hematologic parameters, OS advantage was found to consistently favor CPX-351. Covariates not found to be associated with OS included sex, hemoglobin levels, percentage of bone marrow blasts, and FLT3-ITD mutation positivity.

Patient characteristics were well balanced between the 2 groups, with a median age of 67 years and a majority of patients being men. AML subtypes in the CPX-351 and 7 + 3 arms were therapy-related AML (20% vs 21%, respectively); AML with antecedent myelodysplastic syndrome (MDS), with (33% vs 35%) or without (14% vs 12%) prior hypomethylating agents; AML with antecedent CMML (7% vs 8%); or de novo AML with MDS karyotype (27% vs 24%).

The indicated study led to the approval of CPX-351 in 2017 for the treatment of adults with newly-diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes, 2 disease subtypes known for poor outcomes to therapy.2


  1. Five-Year Final Results of a Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukemia (AML): Outcomes By Age Subgroup and Among Responders. Presented at: 2021 Transplant and Cellular Therapy Meetings of ASTCT and CIBMTR; February 8-12, 2021. Abstract 135.
  2. FDA approves liposome-encapsulated combination of daunorubicin-cytarabine for adults with some types of poor prognosis AML. FDA. August 3, 2017. Accessed February 10, 2021. https://bit.ly/2MRE8cE
Related Videos
Matthew Pierre Deek, MD
Bradford (Brad) S. Hoppe, MD, MPH
Michael Chuong, MD, FACRO,
Jiye Liu, MD
Joshua Richter, MD
Shonali Midha, MD
Uwe Platzbecker, MD, an expert on myelodysplastic syndrome
Experts on myelodysplastic syndrome
Meral Beksac, MD
Related Content