ASCO 2018 | Impact of NGS on treatment selection in AML

The evolution of next-generation sequencing (NGS) and the comprehensive accessibility of novel agents in acute myeloid leukemia (AML) led Rita Elias Assi from University of Texas MD Anderson Cancer Center, Houston, TX, USA, and colleagues to examine how wider use of NGS testing could improve treatment and outcomes of adult AML patients. The findings of the study were presented at an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, USA, on 1–5 June, 2018.

In this retrospective cohort study, 1,470 consecutive AML patients (median age = 63 years, range 18–91) were treated between October 2012 and June 2016 with available NGS data were included in this study. The objectives of this retrospective study were to evaluate the frequency of actionable mutations (any gene alteration potentially targetable directly or a nearby pathway), investigate the impact of NGS on subsequent targeted therapy decision and to study and understand the barriers to enrolment in clinical trials.

Sequencing data obtained on bone marrow (BM) samples at diagnosis were examined for 17 actionable genes including ALK, CSF1R, FGFR1/2/3, FLT3, IDH1/2, JAK2, KDR, KRAS/NRAS, NPM1, PDGFRA, PTPN11, RET and TP53, which were potentially directly or indirectly targeted with standard or investigational agents.

Key findings:

• A median of two (range, 1–5) actionable mutations were identified in 66% (976/1470) of patients
• Following NGS results, 86% (1271/1470) of patients started some form of therapy based
• Overall, 825 (65%) patients were enrolled into 87 available clinical trials
  • Patients who had any actionable mutations were more likely to be treated on a clinical trial, compared to those who did not have any actionable mutation: P < 0.00001
• Patients (n = 976) harboring actionable mutations:
  • 36% were treated on clinical trial
  • 25% received some form of targeted therapy
  • Patients who received targeted therapy were more likely to have relapsed/refractory disease and more likely to be treated on earlier clinical trials, compared to those who did not receive targeted therapy, who were more likely to have newly diagnosed disease and receive more phase II trials
    • Patients receiving targeted therapy showed higher response rates than those who did not at diagnosis
  • Patients with actionable mutations receiving targeted therapy had better relapse-free survival than patients with no actionable mutations

Key limitations of this study includes its retrospective nature, lack of data on variant allele frequency. Additionally, the study was not powered to measure survival. The speaker noted that the results of this study would need to be “contrasted to those conducted at other centers and in community practice”.

Dr. Assi concluded her talk by highlighting the importance of NGS. “NGS can impact therapy decision in more than 30% of AML patients when performed in a timely manner” said the speaker. The findings showed that more patients received targeted novel agents in the relapsed/refractory AML group than in the newly diagnosed group. Dr. Assi further added that “possible reasons are delays in NGS results, urgency to start therapy and presumption that standard therapy may be better than investigational targeted agents.”

Reference

1. Assi R.E. et al. Impact of next-generation sequencing (NGS) on treatment selection in acute myeloid leukemia (AML). Abstract 103. 2018 ASCO Annual Meeting. 2018 June 1–5.