Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial

• Published in: The lancet oncology 2018-12, Vol.19 (12), p.1668-1679
• Main Authors: Platzbecker, Uwe, Prof, Middeke, Jan Moritz, MD, Sockel, Katja, MD, Herbst, Regina, MD, Wolf, Dominik, Prof, Baldus, Claudia D, Prof, Oelschlägel, Uta, PhD, Mütherig, Anke, MD, Fransecky, Lars, MD, Noppeney, Richard, MD, Bug, Gesine, MD, Götze, Katharina S, Prof, Krämer, Alwin, Prof, Bochtler, Tilmann, MD, Stelljes, Matthias, Prof, Groth, Christoph, MD, Schubert, Antje, PhD, Mende, Marika, MD, Stölzel, Friedrich, MD, Borkmann, Christine, MD, Kubasch, Anne Sophie, MD, von Bonin, Malte, MD, Serve, Hubert, Prof, Hänel, Mathias, MD, Dührsen, Ulrich, MD, Schetelig, Johannes, Prof, Röllig, Christoph, MD, Kramer, Michael, MSc, Ehninger, Gerhard, Prof, Bornhäuser, Martin, Prof, Thiede, Christian, Prof
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Bone marrow; Cancer; CD34 antigen; Chemotherapy; Flow cytometry; Hematology; Hematology, Oncology, and Palliative Medicine; Leukemia; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Neutropenia; Patients; Remission; Runx1 protein; Stem cell transplantation; Studies
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(18)30580-1

SummaryBackgroundMonitoring of measurable residual disease (MRD) in patients with advanced myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML) who achieve a morphological complete remission can predict haematological relapse. In this prospective study, we aimed to determine whether MRD-guided pre-emptive treatment with azacitidine could prevent relapse in these patients. MethodsThe relapse prevention with azacitidine (RELAZA2) study is an open-label, multicentre, phase 2 trial done at nine university health centres in Germany. Patients aged 18 years or older with advanced MDS or AML, who had achieved a complete remission after conventional chemotherapy or allogeneic haemopoietic stem-cell transplantation, were prospectively screened for MRD during 24 months from baseline by either quantitative PCR for mutant NPM1, leukaemia-specific fusion genes ( DEK–NUP214, RUNX1–RUNX1T1, CBFb–MYH11), or analysis of donor-chimaerism in flow cytometry-sorted CD34-positive cells in patients who received allogeneic haemopoietic stem-cell transplantation. MRD-positive patients in confirmed complete remission received azacitidine 75 mg/m 2 per day subcutaneously on days 1–7 of a 29-day cycle for 24 cycles. After six cycles, MRD status was reassessed and patients with major responses (MRD negativity) were eligible for a treatment de-escalation. The primary endpoint was the proportion of patients who were relapse-free and alive 6 months after the start of pre-emptive treatment. Analyses were done per protocol. This trial is registered with ClincialTrials.gov, number NCT01462578, and finished recruitment on Aug 21, 2018. FindingsBetween Oct 10, 2011, and Aug 20, 2015, we screened 198 patients with advanced MDS (n=26) or AML (n=172), of whom 60 (30%) developed MRD during the 24-month screening period and 53 (88%) were eligible to start study treatment. 6 months after initiation of azacitidine, 31 (58%, 95% CI 44–72) of 53 patients were relapse-free and alive (p