Increase in fetal haemoglobin from baseline to day 10 is a biomarker for response to decitabine in AML : Results of the AML21 randomized phase III trial of the EORTC Leukemia Group, Gruppo Italiano Malattie Ematologiche dell'Adulto ( GIMEMA) and German MDS Study Group

: 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.