EHA 2019 – Outcomes after different intensity of conditioning in acute myeloid leukaemia: the importance of genomic variants

  • Cristina Ferrario — Agenzia Zoe
  • Univadis
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  • In patients with acute myeloid leukaemia (AML) in complete remission (CR) before allogenic hematopoietic cell transplantation (allo-HCT), detection of AML-associated genomic variants was associated with increased relapse rate and lower overall survival (OS) in those randomized to reduced intensity conditioning (RIC) compared to those receiving myeloablative conditioning (MAC).
  • Interventions for AML patients with measurable residual disease (MRD) can result in improved survival.

Why this matters

  • AML patients are at risk of relapse after allo-HCT and MRD status before transplant has been shown to be prognostic.
  • The randomized, phase 3 trial BTN CTN 0901 compared outcomes by conditioning intensity showing a survival benefit in patients receiving MAC, with over half of the patients receiving RIC relapsing within 18 months after transplant.
  • It is currently unknown if modulating the intensity of conditioning in patients positive for MRD can prevent relapse and improve survival.

Study design

  • Pre-transplant blood samples from 188 adult AML patients from BTN CTN 0901 trial were tested using ultra-deep next-generation DNA sequencing (udNGS).
  • MAC and RIC regimens were equally represented and patients were well matched for baseline characteristics.
  • The aim of the study was to determine whether a higher intensity conditioning in patients with genomic evidence of residual disease before allo-HCT improves outcomes after the transplant.

Key results

  • 31% of MAC and 33% of RIC patients did not show AML-associated genomic variants in pre-transplant blood samples and had similar OS at 3 years.
  • When detectable genomic variants were present, survival was significantly different between MAC and RIC arms (3-years OS: 61% vs. 44%, respectively; p=0.02).
  • In multivariate analysis for patients with detectable variants, adjusting for disease risk and donor group, RIC was associated with increased relapse (HR 5.98, p