AML: Somatic Mutation Clearance May Be Prognostic for Survival

The clearance of somatic mutations, particularly in nonpreleukemic genes, is associated with improved overall survival (OS) and a reduced risk of relapse among patients with acute myeloid leukemia (AML) who undergo intensive induction chemotherapy (IIC), according to a study published in the Journal of Clinical Oncology.¹

For this study, researchers enrolled 131 patients with AML who underwent IIC and reached a morphologic complete response (CR) within 30 days of treatment, and for whom pretreatment and CR bone marrow were available for analysis. Participants received frontline idarubicin plus cytarabine-based IIC.

The researchers determined 3 levels of somatic mutation clearance (MC) based on variant allele frequency (VAF) of residual mutations at CR: “MC2.5: if the VAF of residual mutations was < 2.5%; MC1.0: if the VAF was < 1%; and complete MC [CMC].”

Patients who had MC1.0 or CMC had significantly improved outcomes: patients with MC1.0 had a 2-year OS rate of 75% compared with 61% among non-MC1.0 patients (P = .0465); the 2-year OS rate among patients with CMC was 77% compared with 60% among non-CMC patients (P = .0303).

The 2-year cumulative incidence of relapse (CIR) was also significantly reduced, at 26% vs 46% among MC1.0 and non-MC1.0 (P = .0349) patients, respectively, and 24% vs 46% among CMC vs non-CMC (P = .03) patients, respectively.

No significant differences were, however, observed for OS or CIR when assessed by MC2.5.

Multivariable analysis revealed that patients with CMC also had significantly improved event-free survival (P = .0083), OS (P = .04), and CIR (P < .001), compared with non-CMC patients.

When the DNMT3A, TET2, and ASXL1 mutations (preleukemic mutations believed to not represent residual disease) were removed from the analysis, the prognostic implications of MC were strengthened.

The authors concluded that “MC may be a promising tool with which to identify patients with AML who are at high risk of relapse, and should be explored, along with a flow-[minimal residual disease], as an MRD marker in AML.”

Reference

1. Morita K, Kantarjian HM, Wang F, et al. Clearance of somatic mutations at remission and the risk of relapse in acute myeloid leukemia. J Clin Oncol. 2018 Apr 27. doi: 10.1200/JCO.2017.77.6757 [Epub ahead of print]