CPX-351 in acute myeloid leukemia: can a new formulation maximize the efficacy of old compounds?

ABSTRACT

Introduction: The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications.

Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and ‘bridge-to-transplant’ settings. In particular, 60- to 75-year-old patients with secondary AML, when treated with CPX-351, exhibit superior overall survival (HR = 0.69; P = 0.005; median OS 9.56 vs. 5.95 months), event free survival (HR = 0.74; P = 0.021), and composite response rate (47.7% vs. 33.3%; P = 0.016) as compared to standard ‘7 + 3’ therapy. Herein, we detail the main pharmacological features of CPX-351 and review updated results of clinical trials investigating its employment in AML.

Expert commentary: Novel liposome-based drugs display a high therapeutic index and represent a promising alternative to unencapsulated drugs, especially when high-risk features complicate the use of standard treatments. Further efforts in both understanding AML biology and improving nanodrug design are needed.

KEYWORDS:

• Acute myeloid leukemia
• CPX-351
• cytarabine
• daunorubicin
• drug delivery
• liposome
• nanomedicine
• nanoparticles

Information resources

• 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. American Society of Clinical Oncology Meeting, Chicago, IL. June 3–7, 2016.

Synopsis: This phase III study demonstrates CPX-351 efficacy as first-line treatment for elderly patients with secondary AML.

• Shi J, Kantoff PW, Wooster R, et al. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17:20–37.

Synopsis: This review summarizes the latest developments in cancer nanomedicine, discussing novel nano-bio interactions and nanodrug engineering strategies.

• Bose P, Vachhani P, Cortes JE. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options Oncol. 2017;18:17.

Synopsis: This review summarizes some of the most notable recent advances in the treatment of relapse/refractory AML, with a focus on those with the most mature or promising clinical data.

Acknowledgments

The authors would like to thank Mary V.C. Pragnell for writing assistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.