Longer Follow-Up Finds Improved Overall Survival With CPX-351 in Patients With Acute Myeloid Leukemia

The 5-year overall survival was 18% in the CPX-351 group compared to 8% in the standard chemotherapy group.

New study analysis has found improved overall survival (OS) rates in patients with acute myeloid leukemia (AML) who received CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio.1

Daunorubicin and cytarabine are both used as standard induction therapies in patients with AML. To investigate the use of CPX-351 in this patient population, researchers conducted a randomized, open-label, multicenter, phase 3 trial across 39 academic and regional cancer centers in the United States and Canada.1 Primary findings from the trial supported the 2017 FDA approval of the fixed combination in patients 60 to 75 years of age with newly diagnosed high-risk or secondary AML, according to reporting by OncLive.2

Participants were between 60 and 75 years of age with a pathological diagnosis of AML and had received no previous induction therapy. They were randomly assigned 1:1 to receive up to 2 induction cycles of CPX-351 (100 units/m2 on days 1, 3, and 5; on days 1 and 3 for the second induction) or standard chemotherapy (cytarabine 100 mg/m2 per day for 7 days plus intravenous daunorubicin 60 mg/m2 on days 1, 2, and 3; cytarabine for 5 days and daunorubicin on days 1 and 2 for the second induction).1

Patients with complete remission or complete remission with incomplete neutrophil or platelet recovery could receive up to 2 cycles of consolidation therapy with CPX-351 or chemotherapy. The primary outcome of the trial was OS in all randomly assigned patients.1

Between December 2012 and November 2014, 309 patients with newly diagnosed high-risk or secondary AML were enrolled and randomly assigned to receive either CPX-351 or standard chemotherapy.1 At a median follow-up of 60.91 months in the CPX-351 group, the median OS was 9.33 months compared to 5.95 months in the standard chemotherapy group at a median follow-up of 59.93 months.1

The 5-year OS was 18% in the CPX-351 group, compared to 8% in the standard chemotherapy group.1 The trial results also demonstrated encouraging 3-year OS estimates, according to OncLive. The 3-year OS rate was 21% with CPX-351, compared to 9% with standard chemotherapy. A multivariable analysis found that better ECOG performance status, favorable- or intermediate-risk karyotype, lower white blood cell count, higher platelet count, and treatment with CPX-351 were associated with improved OS.2

The most common cause of death in both arms was progressive leukemia, with 124 deaths in the CPX-351 group and 74 out of 140 total deaths in the standard chemotherapy group. Six (5%) of the 124 deaths in the CPX-351 group and 7 (5%) of the 140 deaths in the standard chemotherapy group were considered related to the study group.1

Causes of death that were potentially related to the study treatment include sepsis (n=2), cerebral hemorrhage (n=2), multiorgan failure (n=1), and pneumonia (n=1) in the CPX-351 treatment arm. They included respiratory failure (n=2), sepsis (n=1), pulmonary hemorrhage (n=1), brain hemorrhage (n=1), cardiac arrest (n=1), and multiorgan failure (n=1) in the standard chemotherapy arm.2

This improved OS was maintained after 5 years of follow-up in the CPX-351 arm, which the investigators said supports the earlier evidence that CPX-351 can contribute to long-term remission and improved OS.1

REFERENCES

1. Lancet J, Uy G, Newell L, Lin T, Ritchie E, and Stuart R. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia: 5-year results of a randomized, open-label, multicenter, phase 3 trial. The Lancet Hematology; July 2021. Accessed July 6, 2021. https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(21)00134-4/fulltext?rss=yes

2. Seymour C. CPX-351 Delivers Durable Improvement in OS in Older Patients With AML in Longer Follow-up. OncLive; June 30, 2021. Accessed July 6, 2021. https://www.onclive.com/view/cpx-351-delivers-durable-improvement-in-os-in-older-patients-with-aml-in-longer-follow-up