Emerging therapeutic drugs for AML

Abstract

Multiple new drugs are being developed to treat acute myeloid leukemia (AML), including novel formulations of traditional chemotherapy-antibody drug conjugates and agents that target specific mutant enzymes. Next-generation sequencing has allowed us to discover the genetic mutations that lead to the development and clinical progression of AML. Studies of clonal hierarchy suggest which mutations occur early and dominate. This has led to targeted therapy against mutant driver proteins as well as the development of drugs such as CPX-351 and SGN-CD33A whose mechanisms of action and efficacy may not be dependent on mutational complexity. In this brief review, we discuss drugs that may emerge as important for the treatment of AML in the next 10 years.

Trial registration: ClinicalTrials.gov NCT01696084.

Figure 1

CPX-351 vs 7+3 (7 days of cytarabine and 3 days of daunorubicin). OS for patients with secondary AML. Numbers in parentheses represent confidence intervals. Reprinted from Ravandi et al with permission.

Figure 2

OS in VALOR trial (intention to treat population). HR, hazard ratio.

Figure 3

OS estimates according to randomization and European Leukemia Net genetic group. (A) Favorable and intermediate I/II groups. Median OS times for patients who received LDC (n = 28) and LDC + volasertib (n = 22) were 7.8 and 9.8 months, respectively (HR, 0.54; 95% confidence interval [CI], 0.29-1.02). (B) Adverse group. Median OS times for patients who received LDC (n = 14) and LDC + volasertib (n = 14) were 3.3 and 5.9 months, respectively (HR, 0.63; 95% CI, 0.29-1.40). Database snapshot November 7, 2013.