Secondary acute myeloid leukaemia (sAML) arising from prior myeloid neoplasia or after anticancer therapy accounts for ~25% of AML cases and has a poor prognosis. Nevertheless, the ‘7 + 3’ cytarabine and daunorubicin regimen has remained the standard induction therapy for >40 years. Now, the improved efficacy of a nanoparticle formulation of cytarabine and daunorubicin, CPX-351, in older patients (aged 60–75 years) with sAML — who have particularly dismal outcomes with 7 + 3 therapy — has been confirmed in a phase III trial.

CPX-351 consists of cytarabine and daunorubicin encapsulated in liposomes at a 5:1 synergistic molar ratio. The phase III trial of this agent was conducted to validate an overall survival (OS) benefit for older patients with newly diagnosed sAML observed in a prior randomized phase II trial. In the phase III trial, the median OS duration in the CPX-351 group (n = 153) was 9.6 months versus 6.0 months in the 7 + 3 group (n = 156; HR 0.69; 95% CI 0.52–0.90; P = 0.003); estimated 2-year OS was 31.1% versus 12.3%. Correspondingly, patients in the CPX-351 group were more likely to achieve remission (47.7% versus 33.3%) and to undergo allogeneic haematopoietic stem cell transplantation (34% versus 25%), with the results of an exploratory analysis of survival after transplantation favouring CPX-351 (HR 0.46, 95% CI 0.24–0.89; P = 0.009). Subgroup analyses suggested fairly consistent OS benefits across most subgroups, although prior exposure to hypomethylating agents seemed to reduce the likelihood of benefit from CPX-351.

In agreement with the prolonged plasma circulation and drug exposure of CPX-351, neutrophil and platelet recovery times were delayed relative to those observed with the 7 + 3 regimen. Nevertheless, the overall safety profiles of the two treatments were similar.

In August 2017, CPX-351 became the first FDA-approved treatment for sAML on the basis of these data.