Increase in fetal haemoglobin from baseline to day 10 is a biomarker for response to decitabine in
AML
: Results of the
AML21
randomized phase
Julia Stomper, Michal Kicinski, Tobias Ma, Thomas Meyer, Sylvain Chantepie, Richard Noppeney, Mario Luppi, Ernesta Audisio, Laimonas Griškevičius, Andreas Neubauer, Robin Foà, Walter J. F. M. Van der Velden, Anna Candoni, Radovan Vrhovac, Gianluca Gaidano, Catharina Van Elssen, Mels Hoogendoorn, Maurizio Musso, Attilio Olivieri, Christian Junghanß, Emmanuel Bissé, Stephanie Antunes, Frédéric Baron, Adriano Venditti, Joop H. Jansen, Pierre W. Wijermans, Gerwin Huls, Michael Lübbert Summary
Lack of response or delayed response to therapy are major challenges in the use of DNA‐hypomethylating agents (HMA) in patients with acute myeloid leukaemia (AML). Fetal haemoglobin (HbF) is a potential biomarker for response to HMA treatment but has only been studied in small single‐centre studies. We investigated the association between HbF and treatment outcome in the randomized phase 3 European Organisation for Research and Treatment of Cancer (EORTC)‐1301 trial AML21, which included 606 fit, older AML patients who received 10‐day decitabine or ‘3 + 7’ chemotherapy as induction. HbF was measured twice in the decitabine arm ( n = 135) and at baseline in the 3 + 7 arm ( n = 97). In the decitabine arm, HbF increase from baseline to day 10 was associated with increased odds of reaching complete remission (CR) or CR with incomplete count recovery (CRi) (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.15–5.02, p = 0.020). The hazard ratio (HR) for death comparing patients with HbF increase to those without was 0.83 (95% CI 0.55–1.28, p = 0.40). Baseline HbF in the decitabine arm was not associated with CR/CRi (OR 0.89, 95% CI 0.45–1.75, p = 0.73) or overall survival (HR 0.86, 95% CI 0.58–1.28, p = 0.47). In conclusion, this large prospective study adds to the body of evidence that HbF is an easy‐to‐measure early biomarker for response to HMA treatment.